Ion mobility spectrometer instrument and method of operation

ABSTRACT

An ion mobility spectrometer instrument has a drift tube that is partitioned into a plurality of cascaded drift tube segments. A number of electric field activation sources may each be coupled to one or more of the plurality of drift tube segments. A control circuit is configured to control operation of the number of electric field activation sources in a manner that sequentially applies electric fields to the drift tube segments to allow only ions having a predefined ion mobility or range of ion mobilities to travel through the drift tube. The drift tube segments may define a linear drift tube or a closed drift tube with a continuous ion travel path. Techniques are disclosed for operating the ion mobility spectrometer to produce highly resolved ion mobility spectra.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation-in-part of U.S. patentapplication Ser. No. 12/357,198, filed Jan. 21, 2009, which claims thebenefit of, and priority to, U.S. Provisional Patent Application Ser.No. 61/021,785, the disclosures of which are incorporated herein byreference.

GOVERNMENT RIGHTS

This invention was funded in part by grants from National Institute ofHealth, NIH (Grant Nos. Ag-024547-01 and P41-RR018942); the UnitedStates Government may have rights in this invention.

FIELD OF THE INVENTION

The present invention relates generally to ion separation instruments,and more specifically to instruments that operate to separate ions intime as a function of ion mobility.

BACKGROUND

Ion mobility spectrometers are analytical instruments that are used toseparate ions in time as a function of ion mobility. It is desirable tobe able to control electric fields applied to such instruments in orderto investigate properties of charged particles.

SUMMARY

The present invention may comprise one or more of the features recitedin the attached claims, and/or one or more of the following features andcombinations thereof. An ion mobility spectrometer instrument maycomprise a drift tube partitioned into a plurality of cascaded drifttube segments, each defining an ion inlet at one end and an ion outletat an opposite end, with an ion elimination region defined between theion outlet and an ion inlet of each adjacent drift tube segment. The ionelimination region of a last one of the drift tube segments may becoupled to the ion inlet of a first one of the drift tube segments suchthat the drift tube defines therein a closed and continuous ion travelpath. An ion entrance drift tube segment may have an ion inlet coupledto an ion source and an ion outlet coupled to one of the plurality ofcascaded drift tube segments, and an ion exit drift tube segment mayhave an ion inlet coupled to the one or another one of the plurality ofdrift tube segments, and an ion outlet. An ion gate arrangement may beresponsive to a first set of one or more ion gate signals to direct ionsmoving through the drift tube through the one or another one of theplurality of cascaded drift tube segments while blocking the ions fromentering the ion exit drift tube segment, and to a second set of one ormore ion gate signals to direct the ions moving through the drift tubeinto the ion exit drift tube segment while blocking the ions from movingthrough the one or another one of the plurality of cascaded drift tubesegments. A number, M, of electric field activation sources may each beoperatively connected to one or more of the plurality of drift tubesegments such that, when activated, each establishes a repulsiveelectric field in at least one of the first M ion elimination regionsand in every following Mth ion elimination region, and establishes anelectric drift field in all remaining ion elimination regions and in allof the plurality of cascaded drift tube segments. A control circuit mayinclude a memory having instructions stored therein that are executableby the control circuit to produce the first set of one or more ion gatesignals and sequentially activate each of the number, M, of electricfield activation sources for a time duration while deactivating theremaining number, M, of electric field activation sources to therebycause only ions supplied by the ion source that have a predefined ionmobility or range of ion mobilities defined by the time duration totravel through the drift tube, and after the ions have traveled aroundthe drift tube a selected number of times to produce the second set ofone or more ion gate signals to draw ions moving through the drift tubeout of the drift tube and into the ion exit drift tube segment.

The ion mobility spectrometer may further comprise an ion detectorconfigured to detect ions exiting the ion exit drift tube segment andproduce corresponding ion detection signals. The instructions stored inthe memory may further include instructions executable by the controlcircuit to process the ion detection signals to determine ion mobilityspectral information therefrom.

The ion gate arrangement may comprise a first ion gate positioned in theone or another one of the plurality of cascaded drift tube segments, anda second ion gate positioned in or at the ion inlet of the ion exitdrift tube segment. The first set of one or more ion gate signals maycomprise a first ion gate signal to which the first ion gate isresponsive to allow ions to pass therethrough and a second ion gatesignal to which the second ion gate is responsive to block ions frompassing therethrough, and the second set of one or more ion gate signalsmay comprise a third ion gate signal to which the first ion gate isresponsive to block ions from passing therethrough and a fourth ion gatesignal to which the second ion gate is responsive to allow ions to passtherethrough.

The ion mobility spectrometer may further comprise a voltage supplyoperatively connected to the ion source and to the control circuit. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the voltage source tothereby selectively cause the ion source to produce ions and toselectively supply produced ions to the ion entrance drift tube segment.

The instructions stored in the memory may further include instructionsexecutable by the control circuit to produce the first set of one ormore ion gate signals, to control the ion source to produce ions andcontrol the number, M, of electric field activation sources in a mannerthat allows ions produced by the ion source to enter and fill each ofthe plurality of drift tube segments, to then control the ion source tostop producing ions and sequentially activate each of the number, M, ofelectric field activation sources for the time duration whiledeactivating the remaining number, M, of electric field activationsources to thereby cause only ions within the drift tube that have thepredefined ion mobility or range of ion mobilities defined by the timeduration to travel through the drift tube, and after the ions havetraveled around the drift tube a selected number of times to produce thesecond set of one or more ion gate signals and control the number, M, ofelectric field activation sources to draw ions moving through the drifttube out of the drift tube and into the ion exit drift tube segment. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the number, M, of electricfield activation sources in the manner that allows ions produced by theion source to enter and fill each of the plurality of drift tubesegments by controlling the number, M, of electric field activationsources to pass all ions generated by the ion source from each of theplurality of drift tube segments to the next adjacent drift tubesegment.

The predefined ion mobility or range of ion mobilities may be resonantwith a fundamental frequency defined by the time duration, and theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the number, M, of electricfield activation sources to sweep the time duration between first andsecond predefined time durations to thereby cause ions within the drifttube that have at least one of ion mobilities defined by overtonefrequencies of the time duration and ion mobilities resonant withfundamental frequencies of discrete time durations between the first andsecond time durations to travel through the drift tube.

The ion mobility spectrometer may further comprise a voltage supplyoperatively connected to the ion source and to the control circuit. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the ion source to produceions by controlling the voltage source to cause the ion source toproduce ions and to supply the produced ions to the ion entrance drifttube segment, and to control the ion source to stop producing ions bycontrolling the voltage source to cause the ion source to stop producingions.

The ion outlet of the ion entrance drift tube segment may be coupled toa first one of the plurality of drift tube segments. The instructionsstored in the memory may further include instructions executable by thecontrol circuit to produce the first set of the one or more gatesignals, and to then control the ion source and the number, M, ofelectric field activation sources to alternately (a) supply ions to thefirst one of the plurality of cascaded drift tube segments via the ionentrance drift tube segment while also advancing ions in even-numberedones of the plurality of drift tube segments to next adjacentodd-numbered ones of the plurality of drift tube segments and blockingadvancement of ions in odd-numbered ones of the plurality of drift tubesegments to next adjacent even-numbered ones of the plurality of drifttube segments, and (b) stop the supply of ions to the first one of theplurality of cascaded drift tube segments via the ion entrance drifttube segment while also advancing ions in odd-numbered ones of theplurality of drift tube segments to next adjacent even-numbered ones ofthe plurality of drift tube segments and blocking advancement of ions ineven-numbered ones of the plurality of drift tube segments to nextadjacent odd-numbered ones of the plurality of drift tube segments, afirst number of times to thereby sequentially add ions selectivelyproduced by the ion source to every other one of the plurality of drifttube segments. The instructions stored in the memory may further includeinstructions that are executable by the control circuit to, after ionsselectively produced by the ion source have been added to every otherone of the plurality of drift tube segments the first number of times,control the ion source to stop producing ions and sequentially activateeach of the number, M, of electric field activation sources for the timeduration while deactivating the remaining number, M, of electric fieldactivation sources to thereby cause only ions within the drift tube thathave the predefined ion mobility or range of ion mobilities defined bythe time duration to travel through the drift tube, and after the ionshave traveled around the drift tube a second number of times to producethe second set of the one or more ion gate signals to draw ions movingthrough the drift tube out of the drift tube and into the ion exit drifttube segment. The ion mobility spectrometer may further comprise avoltage supply operatively connected to the ion source and to thecontrol circuit. The instructions stored in the memory may furtherinclude instructions executable by the control circuit to control theion source to produce ions by controlling the voltage source to causethe ion source to produce ions and to supply the produced ions to theion entrance drift tube segment, and to control the ion source to stopproducing ions by controlling the voltage source to cause the ion sourceto stop producing ions.

An ion mobility spectrometer instrument may comprise a linear drift tubepartitioned into a plurality of cascaded drift tube segments, eachdefining an ion inlet at one end and an ion outlet at an opposite end,with an ion elimination region defined between the ion outlet and an ioninlet of each adjacent drift tube segment. An ion source coupled to theion inlet of a first one of the plurality of cascaded drift tubesegments. A number, M, of electric field activation sources may each beoperatively connected to one or more of the plurality of drift tubesegments such that, when activated, each establishes a repulsiveelectric field in at least one of the first M ion elimination regionsand in every following Mth ion elimination region, and also establishesan electric drift field in all remaining ion elimination regions and inall of the plurality of cascaded drift tube segments. A control circuitmay include a memory having instructions stored therein that areexecutable by the control circuit to sequentially activate each of thenumber, M, of electric field activation sources for a time durationwhile deactivating the remaining number, M, of electric field activationsources to thereby cause only ions supplied by the ion source that havea predefined ion mobility or range of ion mobilities defined by the timeduration to travel through the drift tube from the first drift tubesegment to a last one of the plurality of drift tube segments, and tothen, for a first predefined number of times, sequentially activatingeach of the number, M, of electric field activation sources for the timeduration while deactivating the remaining number, M, of electric fieldactivation sources in reverse order to thereby cause only ions havingthe predefined ion mobility or range of mobilities defined by the timeduration to travel through the drift tube from the last drift tubesegment to the first drift tube segment followed by sequentiallyactivating each of the number, M, of electric field activation sourcesfor the time duration while deactivating the remaining number, M, ofelectric field activation sources to thereby cause only ions having thepredefined ion mobility or range of ion mobilities defined by the timeduration to travel through the drift tube from the first drift tubesegment to the last drift tube segment. Means may be provided forrandomizing positions of the ions within the drift tube during each passof ions from at least one of the first drift tube segment to the lastdrift tube segment and the last drift tube segment to the first drifttube segment.

The ion inlet of the first drift tube segment may comprise an ion gate.The instructions stored in the memory may further include instructionsexecutable by the control circuit to control the ion gate to selectivelyallow entrance of ions generated by the ion source into the ion inlet ofthe first drift tube segment.

The ion source may comprise at least one ion separation instrumentconfigured to separate ions in time as a function of one or moremolecular characteristics. The at least one ion separation instrumentmay include at least one of a liquid chromatograph, a gas chromatograph,an ion mobility spectrometer, a mass spectrometer, and a capillaryelectrophoresis instrument.

The ion mobility spectrometer instrument may further comprise an iondetector configured to detect ions exiting the ion outlet of the lastdrift tube segment and produce corresponding ion detection signals. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to process the ion detection signalsto determine ion mobility spectral information therefrom.

The predefined ion mobility or range of ion mobilities may be resonantwith a fundamental frequency defined by the time duration. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the number, M, of electricfield activation sources to sweep the time duration between first andsecond predefined time durations to thereby cause ions within the drifttube that have at least one of ion mobilities defined by overtonefrequencies of the time duration and ion mobilities resonant withfundamental frequencies of discrete time durations between the first andsecond time durations to travel through the drift tube.

A method of separating ions as a function of ion mobility in a drifttube partitioned into a plurality of cascaded drift tube segments eachdefining an ion inlet at one end and an ion outlet at an opposite end,with an ion elimination region defined between the ion outlet and an ioninlet of each adjacent drift tube segment, may comprise controlling anion source to supply ions to the ion inlet of a first one of theplurality of drift tube segments, sequentially controlling electricfields in each of the plurality of drift tube segments and ionelimination regions for a time duration to cause only ions supplied bythe ion source to the first one of the plurality of drift tube segmentsthat have a predefined ion mobility or range of ion mobilities definedby the time duration to travel through the drift tube from the first oneof the plurality of drift tube segments to a last one of the pluralityof drift tube segments, to then, for a predefined number of times,sequentially control electric fields in each of the plurality of drifttube segments and ion elimination regions in reverse order to cause onlyions having the predefined ion mobility or range of mobilities definedby the time duration to travel through the drift tube from the last oneof the plurality of drift tube segments to the first one of theplurality of drift tube segments drift tube segments followed bysequentially controlling electric fields in each of the plurality ofdrift tube segments and ion elimination regions to cause only ionshaving the predefined ion mobility or range of ion mobilities defined bythe time duration to travel through the drift tube from the first one ofthe plurality of drift tube segments to the last one of the plurality ofdrift tube segments, and randomizing positions of the ions within thedrift tube during each pass of ions from at least one of the first oneof the plurality of drift tube segments to the last one of the pluralityof drift tube segments and the last one of the plurality of drift tubesegments to the first one of the plurality of drift tube segments.

Randomizing positions of the ions within the drift tube may comprisetrapping the ions for a trap period in an ion trap positioned within thedrift tube during each pass of the ions. The trap period may be selectedto allow ions trapped within the ion trap to randomize their positionsrelative to the ion trap. Alternatively or additionally, randomizingpositions of the ions within the drift tube comprises trapping the ionsfor a trap period in a first ion trap positioned adjacent to the lastone of the plurality of drift tube segments during each pass of the ionsfrom the first one of the plurality of drift tube segments to the lastone of the plurality of drift tube segments and trapping the ions forthe trap period in a second ion trap positioned adjacent to the firstone of the plurality of drift tube segments during each pass of the ionsfrom the last one of the plurality of drift tube segments to the firstone of the plurality of drift tube segments, wherein the trap period maybe selected to allow ions trapped within the first and second ion trapsto randomize their positions relative to the first and second ion trapsrespectively. Alternatively or additionally, randomizing positions ofthe ions within the drift tube may comprise progressively diminishingmagnitudes of the electric fields in a number of adjacent ones of theplurality of drift tube segments to cause the ions to randomize bybunching up in at least some of the number of adjacent ones of theplurality of drift tube segments in which the magnitudes of the electricfields are diminished. The number of adjacent ones of the plurality ofdrift tube segments may comprise a first subset of adjacent ones of theplurality of drift tube segments including the first one of theplurality of drift tube segments and a second subset of adjacent ones ofthe plurality of drift tube segments including the last one of theplurality of drift tube segments. Alternatively, the number of adjacentones of the plurality of drift tube segments may include at least one ofthe first one of the plurality of drift tube segments and the last oneof the plurality of drift tube segments.

The predefined ion mobility or range of ion mobilities may be resonantwith a fundamental frequency defined by the time duration. The methodmay further comprise controlling the number, M, of electric fieldactivation sources to sweep the time duration between first and secondpredefined time durations to thereby cause ions within the drift tubethat have at least one of ion mobilities defined by overtone frequenciesof the time duration and ion mobilities resonant with fundamentalfrequencies of discrete time durations between the first and second timedurations to travel through the drift tube.

An ion mobility spectrometer instrument may comprise a linear drift tubepartitioned into a plurality of cascaded drift tube segments, eachdefining an ion inlet at one end and an ion outlet at an opposite end,with an ion elimination region defined between the ion outlet and an ioninlet of each adjacent drift tube segment, an ion source coupled to theion inlet of a first one of the plurality of cascaded drift tubesegments, an ion trap positioned to receive therein ions travelingthrough the drift tube, a number, M, of electric field activationsources each operatively connected to one or more of the plurality ofdrift tube segments such that, when activated, each establishes arepulsive electric field in at least one of the first M ion eliminationregions and in every following Mth ion elimination region, and alsoestablishes an electric drift field in all remaining ion eliminationregions and in all of the plurality of cascaded drift tube segments, anda control circuit including a memory having instructions stored thereinthat are executable by the control circuit to, for a first predefinednumber of times, sequentially activate each of the number, M, ofelectric field activation sources for a time duration while deactivatingthe remaining number, M, of electric field activation sources to therebycause only ions supplied by the ion source that have a predefined ionmobility or range of ion mobilities defined by the time duration totravel through the drift tube followed by controlling the ion trap totrap therein the ions traveling through the drift tube that have thepredefined ion mobility or range of ion mobilities, and to then, for asecond predefined number of times, control the ion trap to release theions trapped therein, to sequentially activate each of the number, M, ofelectric field activation sources for the time duration whiledeactivating the remaining number, M, of electric field activationsources to cause the released ions having the predefined ion mobility orrange of ion mobilities to travel from to one end of the linear drifttube, then back to the other end of the linear drift tube and back tothe ion trap followed by controlling the ion trap to trap the ionstherein for a trap period selected to allow ions trapped within the iontrap to randomize their positions relative to the ion trap, and to thencontrol the ion trap to release the ions trapped therein to an iondetector.

The ion mobility spectrometer may further comprise a voltage supplyoperatively connected to the ion source and to the control circuit. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the voltage source each ofthe first predefined number of times to cause the ion source to produceions and supply the produced ions to the ion inlet of the first one ofthe plurality of drift tube segments.

The ion mobility spectrometer may further comprise a voltage supplyoperatively connected to the ion source and to the control circuit. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the voltage source to causethe ion source to continuously produce ions and supply the produced ionsto the ion inlet of the first one of the plurality of drift tubesegments.

The ion detector may be configured to detect ions released from thefirst ion trap and produce corresponding ion detection signals. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to process the ion detection signalsto determine ion mobility spectral information therefrom.

The plurality of cascaded drift tube segments may comprise a last drifttube segment at an opposite end of the drift tube from the first drifttube segment. The ion trap may be coupled to the ion outlet of the lastdrift tube segment.

The predefined ion mobility or range of ion mobilities may be resonantwith a fundamental frequency defined by the time duration. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the number, M, of electricfield activation sources during the first predefined time period andduring the second predefined time period to sweep the time durationbetween first and second predefined time durations to thereby cause ionswithin the drift that have at least one of ion mobilities defined byovertone frequencies of the time duration and ion mobilities resonantwith fundamental frequencies of discrete time durations between thefirst and second time durations to travel through the drift tube and tobe trapped within the ion trap. In this embodiment, the ion mobilityspectrometer may further comprise a voltage supply operatively connectedto the ion source and to the control circuit, and the instructionsstored in the memory may further include instructions executable by thecontrol circuit to control the voltage source each of the firstpredefined number of times to cause the ion source to produce ions andsupply the produced ions to the ion inlet of the first one of theplurality of drift tube segments. Alternatively, the instructions storedin the memory may include instructions executable by the control circuitto control the voltage source to cause the ion source to continuouslyproduce ions and supply the produced ions to the ion inlet of the firstone of the plurality of drift tube segments.

An ion mobility spectrometer instrument may comprise a linear drifttube, an ion source coupled to the ion inlet of the linear drift tube, afirst ion trap positioned adjacent to the ion inlet of the linear drifttube, a second ion trap positioned adjacent to an ion outlet of thelinear drift tube, the linear drift tube defining a single drift tuberegion between the first and second ion traps, and at least one electricfield activation source operatively connected to the single drift tuberegion. The at least one electric field activation source may becontrollable to establish an electric field in the single drift tuberegion in a first direction that causes ions supplied by the ion sourceto drift from the first ion trap toward the second ion trap andcontrollable to alternatively establish an electric drift field in thesingle drift tube region in a second direction that causes ions suppliedby the ion source to drift from the second ion trap toward the first iontrap. A control circuit may include a memory having instructions storedtherein that are executable by the control circuit to execute a processa predefined number of times. The process may include activating the atleast one electric field activation source for a time duration toestablish an electric field in the first direction to cause only ionssupplied by the ion source that have a predefined ion mobility or rangeof ion mobilities defined by the time duration to travel through thesingle drift tube region in the first direction toward the second iontrap followed by controlling the second ion trap to trap therein theions that have the predefined ion mobility or range of ion mobilities,and then controlling the second ion trap to release the ions trappedtherein and activate the at least one electric field activation sourcefor the time duration to establish an electric field in the seconddirection to cause only ions supplied by the ion source that have thepredefined ion mobility or range of ion mobilities defined by the timeduration to travel through the single drift tube region in the seconddirection toward the first ion trap followed by controlling the firstion trap to trap therein the ions that have the predefined ion mobilityor range of ion mobilities followed by controlling the first ion trap torelease the ions trapped therein.

The instructions stored in the memory may further include instructionsexecutable by the control circuit to control the first and second iontraps to trap ions therein for a trap period, the trap period selectedto allow ions trapped within the first ion trap and the second ion trapto randomize their positions relative to the first and second ion traprespectively.

The ion mobility spectrometer instrument may further comprise an iondetector configured to detect ions exiting the linear drift tube. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the second ion trap torelease ions trapped therein toward the ion detector and to process theion detection signals to determine ion mobility spectral informationtherefrom.

The predefined ion mobility or range of ion mobilities may be resonantwith a fundamental frequency defined by the time duration. Theinstructions stored in the memory may further include instructionsexecutable by the control circuit to control the at least one electricfield activation source to sweep the time duration between first andsecond predefined time durations to thereby cause ions that havefundamental frequencies resonant with each of a number of discrete timedurations between the first and second time durations to travel throughthe single drift tube region, and to execute the process the predefinednumber of times for each of the number of discrete time durationsbetween the first and second predefined time durations.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of one illustrative embodiment of an ionmobility spectrometer instrument.

FIG. 2 is a diagram of one illustrative embodiment of the drift tube andassociated arrangement of the electric field activation sources of theion mobility spectrometer of FIG. 1.

FIG. 3 is a timing diagram illustrating operation of the ion mobilityspectrometer of FIGS. 1 and 2.

FIG. 4A is a diagram of one several cascaded sections of the drift tubeillustrated in FIG. 2.

FIGS. 4B-4D illustrate alternate embodiments of the arrangement of theelectric field activation sources relative to the drift tube of FIG. 4A.

FIG. 5 is a flowchart of one illustrative process for operating the ionmobility spectrometer of either of FIG. 1 or 3 as an ion mobility filteroperable to produce only ions having a selected mobility or range ofmobilities from a continuous or discrete ion source.

FIG. 6 is a plot of ion intensity vs. drift time illustrating the drifttime of ions of the sodiated monomer [M+Na]⁺ form of the simpleoligosaccharide isomer raffinose through one particular embodiment ofthe ion mobility spectrometer of FIG. 1.

FIG. 7 is a flowchart of one illustrative process for operating the ionmobility spectrometer of either of FIG. 1 or 3 by sweeping the pulsewidths of the electric field activation sources over a range of pulsewidth durations.

FIG. 8 is a plot of ion intensity vs. frequency illustrating the resultin the frequency domain of the process of FIG. 7 using a continuoussource of raffinose ions.

FIG. 9 includes a number of plots of ion intensity vs. frequencyillustrating results in the frequency domain of the process of FIG. 7applied to ion mobility instruments having different phase numbers.

FIG. 10 includes a number of plots of ion intensity vs. frequencyillustrating results in the frequency domain of the process of FIG. 5applied to ion mobility instruments having different numbers of drifttube sections.

FIG. 11 includes a number of plots of ion intensity vs. frequencyillustrating results in the frequency domain of the process of FIG. 7applied to a raffinose sample, a melezitose sample and to a samplemixture of raffinose and melezitose.

FIG. 12A includes a number of plots of ion intensity vs. total drifttime illustrating results in the time domain of the process of FIG. 5applied to a raffinose/melezitose mixture using a cyclotron geometry ionmobility spectrometer.

FIG. 12B is a diagram of one illustrative embodiment of a cyclotrongeometry ion mobility spectrometer used to generate the plots of FIG.12A.

FIG. 13 is a block diagram of one illustrative embodiment of a cascadedion mobility spectrometer instrument that employs some of the conceptsillustrated and described with respect to FIGS. 1-12B.

FIG. 14 is a flowchart of one illustrative process for operating the ionmobility spectrometer of FIG. 12B by first pre-filling the drift tubewith ions and then sequentially controlling the electric fieldactivation sources to direct ions some number of revolutions around thedrift tube in a manner that resolves only ions having a selectedmobility or range of mobilities.

FIG. 15 is a flowchart of another illustrative process for operating theion mobility spectrometer of FIG. 12B by sequentially controlling theelectric field activation sources to direct ions having a selectedmobility or range of mobilities around the drift tube while alsoperiodically introducing new ions into the drift tube from the ionsource, and then continuing to sequentially control the electric fieldactivation sources to direct ions having the selected mobility or rangeof mobilities some number of revolutions around the drift tube withoutintroducing new ions into the drift tube such that only ions within thedrift tube having the selected mobility or range of mobilities areresolved.

FIGS. 16A-16L are successive or sequential block diagrams of oneillustrative embodiment of the ion mobility spectrometer of FIG. 12Billustrating operation of the spectrometer during the part of theprocess illustrated in the flowchart of FIG. 15 in which the electricfield activation sources are sequentially controlled to direct ionshaving a selected mobility or range of mobilities around the drift tubewhile also periodically introducing new ions into the drift tube fromthe ion source.

FIG. 17 is a block diagram of another illustrative embodiment of an ionmobility spectrometer instrument.

FIG. 18 is a block diagram of the ion mobility spectrometer of FIG. 1illustrating one illustrative technique controlling electric fieldswithin some of the drift tube segments adjacent to the ion entrance andion exit ends when operating a linear drift tube ion mobilityspectrometer to direct ions back and forth between the two ends of thedrift tube in a manner that resolves only ions having a selectedmobility or range of mobilities.

FIG. 19 is a block diagram of yet another illustrative embodiment of anion mobility spectrometer instrument.

FIG. 20 is a flowchart of one illustrative process for operating the ionmobility spectrometer of FIG. 19 by sequentially controlling theelectric field activation sources to direct ions back and forth betweenthe ends of the drift tube in a manner that resolves only ions having aselected mobility or range of mobilities.

FIG. 21 is a block diagram of still another illustrative embodiment ofan ion mobility spectrometer.

DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to a number of illustrativeembodiments shown in the attached drawings and specific language will beused to describe the same.

Referring to FIG. 1, a block diagram is shown of one illustrativeembodiment of an ion mobility spectrometer instrument 10. In theillustrated embodiment, the ion mobility spectrometer instrument 10includes an ion source 12 having an ion outlet that is couple to an ioninlet of a drift tube 14. An ion outlet of the drift tube 14 is coupledto an ion detector 16 having a signal output that is electricallyconnected to an input of a control circuit 18. The control circuit 18includes a conventional memory unit 20, and further includes aconventional clock circuit 22 that may be controlled by the controlcircuit 18 in a conventional manner to produce periodic signals ofdesired frequency. Illustratively, a source of buffer gas 24 suppliesbuffer gas to the drift tube 14 in a conventional manner.

The control circuit 18 is electrically connected to a control input ofan ion source voltage supply, V_(IS), having a number, K, of outputsthat are electrically connected to the ion source 12, where K may be anypositive integer. The ion source 12 may be any conventional ion sourcethat is configured to controllably produce ions from one or moresamples. The ion source voltage supply, V_(IS), may accordinglyrepresent one or more voltage supplies configured to controllablyproduce, under the control of the control circuit 18 and/or manuallycontrollable or programmable, one or more corresponding voltages forcontrolling operation of the ion source 12 in a conventional manner toproduce ions. Illustratively, the ion source 12 may be configured tocontinuously produce ions, or may alternatively be configured to producediscrete packets of ions. Examples of such conventional ion sourcesinclude, but are not limited to, electrospray ion sources (ESI), ionsources using radiation source to desorb ions from a sample, e.g.,matrix-assisted laser desorption ion sources (MALDI), ion sources thatcollect generated ions in an ion trap for subsequent release, and thelike. Alternatively or additionally, the ion source 12 may be or includeone or more conventional ion separation instruments configured toseparate ions in time as a function of one or more molecularcharacteristics. Examples include, but are not limited to, aconventional liquid or gas chromatograph, a conventional massspectrometer, a conventional ion mobility spectrometer, a capillaryelectrophoresis instrument, or the like. In any case, ions produced bythe ion source 12 exit an ion outlet of the ion source 12 and enter anion inlet of the drift tube 14 of the ion mobility spectrometerinstrument 10.

The ion mobility spectrometer 10 further includes a number, M, ofelectric field activation sources, e.g., voltage sources, V₁-V_(M),where M may be any positive integer greater than 1. In the illustratedembodiment, the control circuit 18 includes a corresponding number ofoutputs, each of which is electrically connected to an input of adifferent one of the electric field activation sources, V₁-V_(M). Inalternate embodiments, the control circuit 18 may include fewer outputsthat are electrically connected to corresponding inputs of fewer of theelectric field activation sources, V₁-V_(M). In such embodiments, someof which will be described in detail hereinafter, one or more of theelectric field activation sources, V₁-V_(M), may be electricallyconnected to corresponding outputs of the control circuit 18 and one ormore others of the electric field activation sources, V₁-V_(M), may betriggered by operation of an adjacent or other ones of the electricfield activation sources, V₁-V_(M), and/or be programmed for specifiedoperation. In any case, the outputs of the voltage sources V₁-V_(M) areelectrically connected to the drift tube 14 in a manner that will befully described in detail hereinafter.

In the illustrated embodiment, the ion detector 16 is conventional andis configured to produce an ion intensity signal that is proportional tothe number of ions that reach, and are detected by, the ion detector 16.The ion intensity signal is supplied to the control circuit 18, whichthen processes the ion intensity signal to produce ion mobility spectralinformation. The memory unit 20 has instructions stored therein that areexecutable by the control circuit 18 to control the operation of thevarious electric field activation sources, V₁-V_(M).

In the embodiment illustrated in FIG. 1, the drift tube 14 ispartitioned into a plurality of cascaded drift tube segments beginningwith a first drift tube segment positioned adjacent to the ion source 12and defining the ion inlet of the drift tube 14, and ending with an Nthdrift tube segment defining the ion outlet of the drift tube 14. Ionsgenerated by the ion source 12 enter the ion inlet of the drift tube 14,and the electric field activation sources, V₁-V_(M), are operated suchthat the electric fields, i.e., drift fields, established in the variousdrift tube segments are modulated at a frequency that allows only ionshaving mobilities that are resonant with the operating conditions todrift through all of the various drift tube segments. In this way, theion mobility spectrometer 10 operates as an ion mobility filter thatfilters out or away all ions except those having ion mobilities that arewithin a specified range of ion mobilities defined by the frequency ofoperation of the electric field activation sources, V₁-V_(M).Additionally, ions drift through the various drift tube segments atfrequencies that are overtones of the frequency of operation of theelectric field activation sources, V₁-V_(M). Thus, the ion mobilityspectrometer 10 may be operated, as will be described in detail herein,to filter away all ions except those having ion mobilities that areresonant with a fundamental frequency, f_(f), and/or associated overtonefrequencies, of operation of the electric field activation sources,V₁-V_(M). Because of the ability to selectively transmit ions indifferent frequency regions, including those associated with higherovertones, the techniques described herein may be referred to asOvertone Mobility Spectrometry (OMS). In this document, the terms“harmonics” should be understood to include the fundamental frequency,f_(f), and integer multiples of the fundamental frequency, and the term“overtone” should be understood to include only the integer multiples ofthe fundamental frequency, f_(f).

Referring now to FIG. 2, a diagram is shown of one illustrativeembodiment of a portion of the drift tube 14 along with one illustrativearrangement of the electric field activation sources of the ion mobilityspectrometer 10 of FIG. 1. In the illustrated embodiment, the drift tube14 is partitioned into a number, N, of cascaded segments, S₁-S_(N),where N may be any positive integer greater than 2, and segments S₁-S₅are shown in FIG. 2. Each of the segments, e.g., S₁-S₅, isillustratively constructed of five concentric, electrically conductiverings, 30 ₁-30 ₅, each separated by a concentric, electricallyinsulating ring 32 ₁-32 ₄ (illustrated in FIG. 2 for the segment S₁only). The first electrically conductive ring, 30 ₁, of each segmentdefines an ion inlet gate, G_(I), to the segment, and the lastelectrically conductive ring, 30 ₅, of each segment defines an ionoutlet gate, G_(O), of the segment. Illustratively, the first and lastrings 30 ₁ and 30 ₅ contain mesh grids, e.g., 90% transmittance Ni meshgrid, although this disclosure contemplates embodiments which do notinclude one or both of the rings 30 ₁ and 30 ₅. In any case, adjacentones of the electrically conductive rings, 30 ₁-30 ₅, are separated byone of the electrically insulating rings, 32 ₁-32 ₄, and adjacentsegments, S₁-S_(N), of the drift tube 14 are separated by a concentric,electrically insulating isolator ring 34, e.g., Teflon®, a syntheticfluoropolymer resin. All of the rings, 30 ₁-30 ₅, 32 ₁-32 ₄ and 34 arestacked together, sealed with O-rings and compressed using a number,e.g., eight, of threaded rods, e.g., nylon. The segments, S₁-S_(N), arethen joined together to form the drift tube 14.

In the illustrated embodiment, a resistor, R, is electrically connectedbetween each of the electrically conductive rings in each drift tubesegment, and a resistor R_(E) is connected between the ion outlet gateand ion inlet gate of each adjacent drift tube segment. The drift tube14 of the ion mobility spectrometer instrument 10 is constructed withthe electrically conductive rings 30 ₁-30 ₅ electrically insulated fromeach other and with the drift tube segments S₁-S_(N) also electricallyisolated from each other so that electric fields can be developedseparately and independently in each of the segments S₁-S_(N) and/or ingroups of the segments S₁-S_(N). By applying suitable voltages acrossthe drift tube segments and/or groups of drift tube segments, as will bedescribed in greater detail hereinafter, uniform electric fields areillustratively established in each drift tube segment in a manner thattransmits ions generated by the ion source 12 through the drift tube 14and through the ion outlet of the last segment S_(N).

The region between the ion inlet gate and the ion outlet gate of eachdrift tube segment defines an ion transmission region of distance,d_(t), and the region between the ion outlet gate of one drift tubesegment and the ion inlet gate of the next adjacent drift tube segmentdefines an ion elimination region of distance, d_(e). Thus, for example,the drift tube segment S₁ has an ion transmission region of distance,d_(t)(1) defined between G_(I1) and G_(O1), and an ion eliminationregion of distance d_(e)(1) defined between G_(O1) and G_(I2).

In one example embodiment, the drift tube 14 is constructed of 21identical drift tube segments as just described, with an ion focusingfunnel (not shown) positioned approximately mid way between the ioninlet and the ion outlet of the drift tube 14. In this exampleembodiment, the ion transmission region, d_(t), and the ion eliminationregion, d_(e), are together 5.84 cm in length, and the total length ofthe 22-section drift tube 14 is 128.5 cm from the ion inlet to the ionoutlet of the drift tube 14. Further details relating to this exampleconstruction of the drift tube 14, including construction of the ionfocusing funnel, are provided in co-pending U.S. Patent Application Pub.No. US 2007/0114382 A2, the disclosure of which is incorporated hereinby reference. It will be understood, however, that this disclosurecontemplates other embodiments in which the drift tube 14 is constructedin accordance with other conventional techniques, portions or theentirety of which may be linear or non-linear. For example, the drifttube 14 may alternatively be provided in the form of a circular orcyclotron drift tube, and further details relating to some examplecircular or cyclotron drift tube arrangements are provided in co-pendingPCT Publication No. WO 2008/028159 A2, filed Aug. 1, 2007, thedisclosure of which is incorporated herein by reference. It will beunderstood, however, that in any such alternate configuration the drifttube will define a number of cascaded drift tube sections such thatelectric fields may be selectively and separately created in individualand/or groups of the drift tube sections.

In the embodiment illustrated in FIG. 2, one illustrative arrangement 40of the electric field activation sources, V₁-V_(M), is shown thatincludes two electric field activation sources, V₁ and V₂, electricallyconnected to the drift tube 14. The control circuit 18 is illustrativelyconfigured to control operation of the electric field activationsources, V₁ and V₂, e.g., in accordance with instructions stored in thememory 20 that are executable by the control circuit 18, in analternating fashion to generate electric fields within the drift tubesegments, S₁-S_(N), which cause ions of a specified range of ionmobilities to drift through the drift tube 14.

In the illustrated embodiment, the electric field activation sources V₁and V₂ are both conventional DC voltage sources that are controllable bythe control circuit 18 to produce a desired DC voltage across the + and− terminals. The + terminals of V₁ and V₂ are both electricallyconnected to the ion inlet gate, G_(I1), of the first drift tubesegment, S₁. The + terminal of V₁ is further electrically connected tothe ion inlet gates of the even-numbered drift tube segments, e.g., tothe ion inlet gate, G_(I2) of the second drift tube segment, S₂, the ioninlet gate, G_(I4), of the fourth drift tube segment, S₄, etc., andthe + terminal of V₂ is further electrically connected to the ion inletgates of the odd-numbered drift tube segments, e.g., to the ion inletgate, G_(I3) of the third drift tube segment, S₃, the ion inlet gate,G_(I5), of the fifth drift tube segment, S₅, etc. The − terminal of V₁is electrically connected to the ion outlet gates of the odd-numbereddrift tube segments, e.g., to the ion outlet gates, G_(O1), G_(O3),G_(O5), etc. of the drift tube segments S₁, S₃, S₅, etc., respectively.The − terminal of V₂ is electrically connected to the ion outlet gatesof the even-numbered drift tube segments, e.g., to the ion outlet gates,G_(O2), G_(O4), G_(O6), etc. of the drift tube segments S₂, S₄, S₆,etc., respectively. With the exception of V₁ connected across the ioninlet and ion outlet gates, G_(I1) and G_(O1) of the first drift tubesegment, S₁, V₁ and V₂ are thus connected across the ion inlet andoutlet gates of alternating, adjacent pairs of drift tube segments. Forexample, V₂ is electrically connected across S₁ and S₂, e.g., betweenG_(I1) and G_(O2), V₁ is electrically connected across S₂ and S₃, e.g.,between G_(I2) and G_(O3), V₂ is electrically connected across S₃ andS₄, e.g., between G_(I3) and G_(O4), etc.

As illustrated in FIG. 2, the voltage sources, V₁ and V₂, whenactivated, produce linear voltage gradients, VG₁ and VG₂ respectively,across the drift tube segments to which they are connected. Equal-valuedresistors, R, are electrically connected across adjacent pairs of theelectrically conductive rings, 30 ₁-30 ₅, of each drift tube segment,S₁-S_(N), and equal-valued resistors, R_(E), are connected between theion outlet gates and ion inlet gates of adjacent pairs of drift tubesegments. The value of R_(E) is selected relative to R (or vice versa)such that the linear voltage gradients, VG₁ and VG₂, establishcorresponding, constant-valued electrical fields across the variousdrift tube segment pairs.

The control circuit 18 is configured to control operation of the voltagesources, V₁ and V₂, by periodically switching one voltage source, V₁,V₂, on while the other voltage source, V₁, V₂, is off. This has theeffect of alternately establishing a constant electric field acrosssequential, cascaded pairs of the drift tube segment, S₁-S_(N). Thisgenerally allows only ions having ion mobilities that match theswitching frequency to traverse each cascaded pair of drift tubesegments. The periodic switching between V₁ and V₂ also establishes arepulsive electric field, i.e., an electric field that is oriented torepel ions traveling in a direction toward the ion detector 16, in theion elimination regions, d_(e), that follow each cascaded pair of drifttube segments. To illustrate this repulsive electric field, consider thecase when V₁ is off and V₂ is on so that only the voltage gradients VG₂of FIG. 2 exist. Ions entering the first drift tube segment S₁ willdrift under the constant electric field established by VG₂ while V₂ ison. However, ions that reach G_(O2) while V₂ is still on will befiltered out by the repulsive electric field, e.g., reverse electricfield, established between the high +V₂ potential at the ion inlet gateG_(I3) and the low −V₂ potential at the ion outlet gate G_(O2).Generally, V₂ establishes, when activated, repulsive electric fields inthe ion elimination regions d_(e) between the ion outlet gates ofeven-numbered drift tube segments and the ion inlet gates of the nextsequential, odd-numbered drift tube segments, and V₁ likewiseestablishes, when activated, identical repulsive electric fields in theion elimination regions d_(e) between the ion outlet gates ofodd-numbered drift tube segments and the ion inlet gates of the nextsequential, even-numbered drift tube segments. This periodic traversalof two drift tube segments and ion elimination in the activated ionelimination regions, d_(e), causes only ions having ion mobilities thatdrift in the established electric fields at the rate defined by the V₁,V₂ switching rate and overtones thereof to drift through the length ofthe drift tube 14 to the ion detector 16. Generally, if the switchingrate between V₁ and V₂ is constant, this switching rate defines afundamental frequency, f_(f), at which ions of a corresponding range ofmobilities can travel progressively through the drift tube segmentsS₁-S_(N). Alternatively or additionally, if the switching rate is sweptover a range of switching rates, ions having the corresponding range ofion mobilities will also travel progressively through the drift tubesegments S₁-S_(N) at overtone frequencies of the fundamental frequency,f_(f).

Referring now to FIG. 3, a number of plots A-F are shown demonstratingthe progression of ions through the first five segments, S₁-S₅ of thedrift tube 14 of FIGS. 1 and 2 when the voltage sources V₁ and V₂ arealternatively switched on and off. In the example illustrated in FIG. 5,the ion source 12 is configured to continually produce ions 50. Plot Aillustrates the condition when V₁ and V₂ are both initially off. Plot Billustrates the condition when V₁ is subsequently turned on while V₂remains off, which establishes a constant-valued electric field, E₁, inthe ion transmission regions d_(t) of each of the drift tube segments,S₁-S₅, and also in the even-numbered ion elimination regions d_(e)(2)and d_(e)(4), and which establishes a repulsive electric field in theodd-numbered ion elimination regions d_(e)(1), d_(e)(3) and d_(e)(5). Aportion 51 of the continually generated ions 50 drift through d_(t)(1)under the influence of the electric field E₁ toward d_(t)(2). However,ions that arrive at the ion elimination region d_(e)(1) before V₁ isswitched off are filtered out of the ions 51 by the repulsive fieldestablished in the ion elimination region d_(e)(1) by V₁. It will beunderstood that the voltage applied by V₁ across the first drift tubesegment, S₁, will be different than that applied across remaining pairsof the drift tube segments as illustrated in FIG. 2. Generally, thevoltage applied by V₁ across the first drift tube segment, S₁, will beselected so as to establish an electric field, E₁, in the iontransmission region d_(t)(1) that is identical to the electric field E₁established across various pairs of the remaining drift tube segments,S₂-S_(N).

Plot C illustrates the condition when V₁ is switched off and V₂ isswitched on, which establishes a constant-valued electric field, E₂(E₂=E₁), in the ion transmission regions d_(t) of each of the drift tubesegments, S₁-S₅, and also in the odd-numbered ion elimination regionsd_(e)(1), d_(e)(3) and d_(e)(5), and which establishes a repulsiveelectric field in the even-numbered ion elimination regions d_(e)(2) andd_(e)(4). The portion of ions 51 in the d_(t)(1) region continues toadvance under the influence of the electric field E₂ through d_(t)(2)toward d_(t)(3), and another portion 52 of the continually generatedions 50 drifts through d_(t)(1) under the influence of the electricfield E₂ toward d_(t)(2). Ions that arrive at the ion elimination regiond_(e)(2) before V₂ is switched off are filtered out of the ions 51 bythe repulsive field established in the ion elimination region d_(e)(2)by V₂.

Plot D illustrates the condition when V₂ is switched off and V₁ isswitched back on, which establishes the constant-valued electric fieldE₁ as described with respect to plot B. The portion of ions 51 in thed_(t)(2) region continues to advance under the influence of the electricfield E₁ through d_(t)(3) toward d_(t)(4), and another portion 53 of thecontinually generated ions 50 drifts through d_(t)(1) under theinfluence of the electric field E₁ toward d_(t)(2). However, the ions 52that were previously in the d_(t)(1) region are filtered away by therepulsive electric field established in the ion elimination regiond_(e)(1) and therefore do not advance to d_(t)(2), and ions that arriveat the ion elimination regions d_(e)(1) and d_(e)(3) before V₁ isswitched off are filtered out of the ions 53 and 51 respectively by therepulsive field established in the ion elimination regions d_(e)(1) andd_(e)(3) respectively.

Plot E illustrates the condition when V₁ is again switched off and V₂ isswitched back on, which establishes the constant-valued electric field,E₂ described with respect to plot C. The portion of ions 51 in thed_(t)(3) region continues to advance under the influence of the electricfield E₂ through d_(t)(4) toward d_(t)(5), the portion of ions 53 in thed_(t)(1) region continues to advance under the influence of the electricfield E₂ through d_(t)(2) toward d_(t)(3), and yet another portion 54 ofthe continually generated ions 50 drifts through d_(t)(1) under theinfluence of the electric field E₂ toward d_(t)(2). Ions that arrive atthe ion elimination regions d_(e)(2) and d_(e)(4) before V₂ is switchedoff are filtered out of the ions 53 and 51 respectively by the repulsivefield established in the ion elimination regions d_(e)(2) and d_(e)(4)respectively.

Plot F illustrates the condition when V₂ is again switched off and V₁ isswitched back on, which establishes the constant-valued electric fieldE₁ as described with respect to plot B. The portion of ions 51 in thed_(t)(4) region continues to advance under the influence of the electricfield E₁ through d_(t)(5) toward the next drift tube segment (S₆), theportion of ions 53 in the d_(t)(2) regions continues to advance underthe influence of the electric field E₁ through d_(t)(3) toward d_(t)(4),and yet another portion 55 of the continually generated ions 50 driftsthrough d_(t)(1) under the influence of the electric field E₁ towardd_(t)(2). The ions 54 that were previously in the d_(t)(1) region arefiltered away by the repulsive electric field established in the ionelimination region d_(e)(1) and therefore do not advance to d_(t)(2),and ions that arrive at the ion elimination regions d_(e)(3) andd_(e)(5) before V₁ is switched off are filtered out of the ions 53 and51 respectively by the repulsive fields established in the ionelimination regions d_(e)(3) and d_(e)(5) respectively.

While the embodiment of the drift tube 14 of FIG. 2 was illustrated anddescribed as including an arrangement 40 of electric field activationsources in the form of two DC voltage sources, V₁ and V₂, it will beunderstood that this disclosure is not so limited and that embodimentsare contemplated in which the arrangement of electric field activationsources includes more than two voltage sources. Referring now to FIGS.4A-4D, for example, a number of voltage gradient plots are shown, inrelation to the first eight cascaded segments, S₁-S₈, of the drift tube14, that illustrate alternative embodiments in which the arrangement ofelectric field activation sources include additional voltage sources. Asa reference, the voltage gradient plot 40 of FIG. 4B, illustrates theembodiment just described in which the arrangement of electric fieldactivation sources includes two voltage sources V₁ and V₂ connected andconfigured to produce the two illustrated voltage gradients VG₁ and VG₂.

The voltage gradient plot 60 of FIG. 4C, in contrast, illustrates anembodiment in which the arrangement of electric field activation sourcesincludes three voltage sources, V₁, V₂ and V₃, each illustrativelyidentical to the voltage sources V₁ and V₂ illustrated and describedwith respect to FIG. 2. In the embodiment of FIG. 4C, +V₁, +V₂ and +V₃are all electrically connected to the ion inlet gate G_(I1) of the firstdrift tube segment, S₁. The +V₁ is further electrically connected to theion inlet gates G_(I2), G_(I5) and G_(I8), of the drift tube segmentsS₂, S₅ and S₈ respectively, the +V₂ is further electrically connected tothe ion inlet gates G_(I3), and G_(I6), of the drift tube segments S₃and S₆ respectively, and the +V₃ is further electrically connected tothe ion inlet gates G_(I4), and G_(I4), of the drift tube segments S₄and S₇ respectively. The −V₁ is electrically connected to the ion outletgates G_(O1), G_(O4) and G_(O7), the −V₂ is electrically connected tothe ion outlet gates G_(O3), G_(O5) and G_(O8), and the −V₃ iselectrically connected to the ion outlet gates G_(O3) and G_(O6). In thethree voltage source arrangement, the voltage sources V₁-V₃ are thuselectrically connected, in alternating fashion, across three consecutivedrift tube segments with all three voltage sources electricallyconnected to the ion inlet grid G_(I1) of the first drift tube segment,S₁, and then with V₁ electrically connected across S₁, S₂-S_(a), andS₅-S₇, with V₂ electrically connected across S₁-S₂, S₃-S₅ and S₆-S₈ andwith V₃ electrically connected across S₁-S₃ and S₄-S₇.

In operation, the control circuit 18 controls the voltage sources V₁-V₃by sequentially switching one voltage source on for a specified durationwhile maintaining the other two voltage sources in their off state forthat duration. As illustrated in FIG. 4C, for example, the controlcircuit 18 turns on V₁ for the specified duration while maintaining V₂and V₃ in their off states, followed by turning off V₁ and turning on V₂while maintaining V₃ in its off state for the specified duration,followed by turning off V₂ and turning on V₃ while maintaining V₁ in itsoff state for the specified duration. The control circuit 18 repeats theabove process many times to cause ions having mobilities related to thevoltage source switching frequency to drift through the various drifttube segments. It will be understood that the voltage applied by V₁across the first drift tube segment, S₁, will be different than thatapplied by V₁ across remaining triplets of the drift tube segments, andthat the voltage applied by V₂ across the first two drift tube segments,S₁-S₂, will also be different than that applied by V₂ across remainingtriplets of the drift tube segments. Generally, the voltage applied byV₁ across the first drift tube segment, S₁, will be selected so as toestablish an electric field, E₁, in the ion transmission region d_(i)(1)that is identical to the electric field E₁ established by V₁ acrossvarious triplets of the remaining drift tube segments, S₂-S_(N), and thevoltage applied by V₂ across the first two drift tube segment, S₁-S₂,will be selected so as to establish an electric field, E₂, in the iontransmission region d_(t)(1), ion elimination region d_(e)(1) and iontransmission region d_(t)(2) that is identical to the electric field E₂established by V₂ across various triplets of the remaining drift tubesegments, S₃-S_(N).

The voltage gradient plot 70 of FIG. 4D illustrates an embodiment inwhich the arrangement of electric field activation sources includes fourvoltage sources, V₁, V₂, V₃ and V₄, each illustratively identical to thevoltage sources V₁ and V₂ illustrated and described with respect to FIG.2. In the embodiment of FIG. 4D, +V₁, +V₂, +V₃ and +V₄ are allelectrically connected to the ion inlet gate G_(I1) of the first drifttube segment, S₁. The +V₁ is further electrically connected to the ioninlet gates G_(I2) and G_(I6), of the drift tube segments S₂ and S₆respectively, the +V₂ is further electrically connected to the ion inletgates G_(I3), and G_(I7), of the drift tube segments S₃ and S₇respectively, the +V₃ is further electrically connected to the ion inletgates G_(I4), and G_(I8), of the drift tube segments S₄ and S₈respectively, and the +V₄ is further electrically connected to the ioninlet gate G_(I5) of the drift tube segment S₅. The −V₁ is electricallyconnected to the ion outlet gates G_(O1) and G_(O5), the −V₂ iselectrically connected to the ion outlet gates G_(O2) and G_(O6), the−V₃ is electrically connected to the ion outlet gates G_(O3) and G_(O7),and the −V₄ is electrically connected to the ion outlet gates G_(O4) andG_(O8). In the four voltage source arrangement, the voltage sourcesV₁-V₄ are thus electrically connected, in alternating fashion, acrossfour consecutive drift tube segments with all four voltage sourceselectrically connected to the ion inlet grid G_(I1) of the first drifttube segment, S₁, and then with V₁ electrically connected across S₁,S₂-S₅, and S₆-S₉, with V₂ electrically connected across S₁-S₂ and S₃-S₆,with V₃ electrically connected across S₁-S₃ and S₄-S₇, and with V₄electrically connected across S₁-S₄ and S₅-S₈.

In operation, the control circuit 18 controls the voltage sources V₁-V₄by sequentially switching one voltage source on for a specified durationwhile maintaining the other three voltage sources in their off state forthat duration. As illustrated in FIG. 4D, for example, the controlcircuit 18 turns on V₁ for the specified duration while maintaining V₂,V₃ and V₄ in their off states, followed by turning off V₁ and turning onV₂ while maintaining V₃ and V₄ in their off states for the specifiedduration, followed by turning off V₂ and turning on V₃ while maintainingV₁ and V₄ in their off states for the specified duration, followed byturning off V₃ and turning on V₄ while maintaining V₁ and V₂ in theiroff states for the specified duration. The control circuit 18 repeatsthe above process many times to cause ions having mobilities related tothe voltage source switching frequency to drift through the variousdrift tube segments. It will be understood that the voltage applied byV₁ across the first drift tube segment, S₁, will be different than thatapplied by V₁ across remaining quadruplets of the drift tube segments,the voltage applied by V₂ across the first two drift tube segments,S₁-S₂, will be different than that applied by V₂ across remainingquadruplets of the drift tube segments, and the voltage applied by V₃across the first three drift tube segments, S₁-S₃, will be differentthan that applied by V₃ across remaining quadruplets of the drift tubesegments. Generally, the voltage applied by V₁ across the first drifttube segment, S₁, will be selected so as to establish an electric field,E₁, in the ion transmission region d_(t)(1) that is identical to theelectric field E₁ established by V₁ across various quadruplets of theremaining drift tube segments, S₂-S_(N), the voltage applied by V₂across the first two drift tube segment, S₁-S₂, will be selected so asto establish an electric field, E₂, in the ion transmission regiond_(t)(1), ion elimination region d_(e)(1) and ion transmission regiond_(t)(2) that is identical to the electric field E₂ established by V₂across various quadruplets of the remaining drift tube segments,S₃-S_(N), and the voltage applied by V₃ across the first three drifttube segment, S₁-S₃, will be selected so as to establish an electricfield, E₃, in the ion transmission regions d_(t)(1), d_(t)(2) andd_(t)(3) and in the ion elimination regions d_(e)(1) and d_(e)(2) thatis identical to the electric field E₃ established by V₃ across variousquadruplets of the remaining drift tube segments, S₄-S_(N).

The number of electric field activation sources, e.g., voltage sources,used in any particular embodiment, and the manner in which they areelectrically connected to the various drift tube segments to operate asdescribed above, is referred to as the phase (φ) of the ion mobilityspectrometer 10. In the example of FIGS. 2, 3 and 4B in which twovoltage sources V₁ and V₂ are used as described above, φ=2 as indicatedin the plot 40 of FIG. 4B. In the example of FIG. 4C in which threevoltage sources V₁, V₂ and V₃ are used as described above, φ=3 asindicated in the plot 60 of FIG. 4C. In the example of FIG. 4D in whichfour voltage sources V₁, V₂, V₃ and V₄ are used as described above, φ=4as indicated in the plot 70 of FIG. 4D. It will be noted from FIG. 3that in a φ=2 system, the fill rate of ions in the various drift tubesegments S₁-S_(N), i.e., the duty cycle of the ion mobility spectrometer10, is 50%. It can be shown that in a φ=3 system, the duty cycle of theion mobility spectrometer is 66.67% and in a φ=4 system, the duty cycleof the ion mobility spectrometer is 75%. A general expression for theduty cycle, d, of the ion mobility spectrometer 10 as a function of thephase, φ, is thus d=1−(1/φ).

Referring again to FIG. 3, the electric fields in the drift tube 14 in atwo-phase (φ=2) ion mobility spectrometer 10 are established by twosource V₁ and V₂. The electric fields established in the drift tube 14by activation of V₁ include an electric drift field E₁, i.e., anelectric field through which ions generated by the ion source drifttoward the ion detector 16, in each of the drift tube segments, i.e., ineach of the ion transmission regions d_(t), and also in theeven-numbered ion elimination regions, d_(e)(2), d_(e)(4), etc., andalso includes a repulsive electric field, i.e., an electric field thatrepels and filters away ions traveling in the direction of the electricdrift field, in odd-numbered ion elimination regions, d_(e)(1),d_(e)(3), d_(e)(5), etc. Similarly, the electric fields established inthe drift tube 14 by activation of V₂ includes an electric drift fieldE₂ in each of the drift tube segments and also in the odd-numbered ionelimination regions, d_(e)(1), d_(e)(3), d_(e)(5), etc., and alsoincludes a repulsive electric field in even-numbered ion eliminationregions, d_(e)(2), d_(e)(4), etc.

It can be shown that in three-phase systems (φ=3) that include threeelectric field activation sources, V₁-V₃, such as that illustrated inFIG. 4C, activation of V₁ establishes a repulsive electric field in thefirst ion elimination region, d_(e)(1), and in every following 3^(rd)ion elimination region, d_(e)(4), d_(e)(7), d_(e)(10), etc., and alsoestablishes an electric drift field, E₁, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₂ likewise establishes a repulsive electric field in thesecond ion elimination region, d_(e)(2), and in every following 3^(rd)ion elimination region, d_(e)(5), d_(e)(8), d_(e)(11), etc., and alsoestablishes an electric drift field, E₂, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₃ similarly establishes a repulsive electric field in thethird ion elimination region, d_(e)(3), and in every following 3^(rd)ion elimination region, d_(e)(6), d_(e)(9), d_(e)(12), etc., and alsoestablishes an electric drift field, E₃, in all remaining ionelimination regions and in all of the drift tube segments d_(t).

It can also be shown that in four-phase systems (φ=4) that include fourelectric field activation sources, V₁-V₄, such as that illustrated inFIG. 4D, activation of V₁ establishes a repulsive electric field in thefirst ion elimination region, d_(e)(1), and in every following 4^(th)ion elimination region, d_(e)(5), d_(e)(9), d_(e)(13), etc., and alsoestablishes an electric drift field, E₁, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₂ likewise establishes a repulsive electric field in thesecond ion elimination region, d_(e)(2), and in every following 4^(th)ion elimination region, d_(e)(6), d_(e)(10), d_(e)(14), etc., and alsoestablishes an electric drift field, E₂, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Activation of V₃ similarly establishes a repulsive electric field in thethird ion elimination region, d_(e)(3), and in every following 4^(th)ion elimination region, d_(e)(7), d_(e)(11), d_(e)(15), etc., and alsoestablishes an electric drift field, E₃, in all remaining ionelimination regions and in all of the drift tube segments d_(t).Finally, activation of V₄ establishes a repulsive electric field in thefourth ion elimination region, d_(e)(4), and in every following 4^(th)ion elimination region, d_(e)(8), d_(e)(12), d_(e)(16), etc., and alsoestablishes an electric drift field, E₄, in all remaining ionelimination regions and in all of the drift tube segments d_(t).

From the foregoing examples, a generalized characterization can be madefor an M-phase system, i.e., one that includes a number, M, of electricfield activation sources, V₁-V_(M). In such an M-phase system, thenumber, M, of electric field activation sources are each be operativelyconnected to one or more of the plurality of drift tube segments suchthat, when activated, each establishes a repulsive electric field in atleast one of the first M ion elimination regions and in every followingMth ion elimination region, and also establishes an electric drift fieldin all remaining ion elimination regions and in all of the plurality ofcascaded drift tube segments. In operation, the control circuit 18sequentially activates each of the number, M, of electric fieldactivation sources for a time duration while deactivating the remainingnumber, M, of electric field activation sources a number of times tothereby cause only ions generated by the ion source that have apredefined ion mobility or range of ion mobilities to traverse the drifttube 14.

Transmission of ions through the various drift tube segments S₁-S_(N) asjust described is only possible if the mobilities of the ions are inresonance with the switching rates of the electric fields applied by theelectric field activation sources regardless of the phase of thespectrometer 10. In other words, to transmit ions sequentially throughthe various drift tube segments S₁-S_(N) as just described, the ionsmust have mobilities that allow traversal exactly one drift tube segmentin one field application duration. Ions with mobilities that are offresonance either traversing a drift tube segment too quickly or tooslowly are eventually eliminated in one of the ion elimination regionsd_(e). The frequency at which the various electric field activationsources are switched on/off, i.e., the frequency at which the ions haveresonant mobilities, is termed the fundamental frequency, f_(f).

In the above description of the operation of the ion mobilityspectrometer instrument 10, the control circuit 18 is described as beingconfigured to control operation of the electric field activation sourcesV₁-V_(M). Illustratively, the memory unit 20 has instructions storedtherein that are executable by the control circuit 18 to controloperation of the electric field activation sources V₁-V_(M) in thismanner.

In one alternative embodiment, each of the electric field activationsources V₁-V_(M) may be programmable to produce, when triggered by anadjacent, e.g., lower-numbered, one of the electric field activationsources V₁-V_(M), an electric field activation pulse of desiredduration. In this embodiment, each higher-numbered one of the electricfield activation sources V₁-V_(M) may be programmable to be triggeredfor activation by deactivation of an adjacent lower-numbered one of theelectric field activation sources V₁-V_(M). Thus, deactivation of V₁will trigger activation of V₂, deactivation of V₂ will triggeractivation of V₃ (or V₁ again), and so forth. In this embodiment, thecontrol circuit 18 is configured to control operation of the electricfield activation sources V₁-V_(M) only by activating the first one ofthe electric field activation sources V₁-V_(M).

In another alternative embodiment, each of the electric field activationsources V₁-V_(M) may be programmable to produce, when triggered by thecontrol circuit 18, an electric field activation pulse having desiredduration. In this embodiment, the control circuit 18 controls activationtimes of each of the electric field activation sources V₁-V_(M), andonce activated each of the electric field activation sources V₁-V_(M) isoperable to produce a pulse having time duration equal to a programmedpulse duration. In this embodiment, the control circuit 18 is configuredto control operation of the electric field activation sources V₁-V_(M)only by activating at specified times each of the electric fieldactivation sources V₁-V_(M).

It will be understood that while the electric field activation sources,V₁-V_(M) were described as producing DC voltages of programmableduration this disclosure contemplates embodiments in which the electricfield activation sources are configured to produce alternatively shapedelectric field activation pulses. For example, such alternatively shapedelectric field activation pulses may be linear or piece-wise linearpulse shapes, such as triangular or other linear or piece-wise linearshapes, or may be non-linear shapes such as sine-wave, Gaussian or othernon-linear shapes. The corresponding electric fields applied intime-dependent fashion to the various segments S₁-S_(N) of the drifttube 14 as described above may thus be linearly, piece-wise linearly ornon-linearly varying. Alternatively still, different ones and/or blocksof the electric field activation sources V₁-V_(M) may be activated fordifferent durations. Those skilled in the art will recognize that, ingeneral, any one or more of the segments S₁-S_(N) may be operated for aduration that is different than the duration of operation of any one ormore of the remaining ones of the segments S₁-S_(N), and that operationof the ion mobility instrument 10 in this manner will result in amulti-dimensional ion mobility spectrometer instrument, i.e., a drifttube having one or more segments in any location relative to the ioninlet and ion outlet that is/are tuned to pass therethrough only ionshaving a mobility or range of mobilities that is/are different thanthat/those of one or more of the remaining segments.

Referring now to FIG. 5, a flowchart is shown of one illustrativeembodiment of a process 80 for operating the ion mobility spectrometerinstrument 10 to act as an ion mobility filter by allowing travelthrough the drift tube 14 of only ions having a predefined mobility orrange of mobilities as described hereinabove with respect to FIGS. 1-4D.The process 80 illustrated in FIG. 5 may be provided, in whole or inpart, in the form of instructions that are stored in the memory unit 20of the control circuit 18 and that are executable by the control circuit18 to control the ion mobility spectrometer instrument 10 in accordancewith the process 80. The process 80 begins at step 82 where the drifttime, DT, through the drift tube 14 is determined for the samplecomponent of interest. This may be done, for example, by first operatingthe ion drift tube 14 in a conventional manner to determine the drifttime, DT, of the sample component of interest, although otherconventional techniques may be used at step 82 to determine the drifttime, DT, of the sample component of interest. For example, conventionalion mobility spectrometer configurations could be used to determine adrift time, or a drift time could be retrieved from literature, althoughin either case, instrument operating parameters used to determine suchdrift times, e.g., buffer gas pressure, operating temperature, drifttube length, etc., would have to be taken into account to determinecorresponding operating parameters for those of the ion mobilityspectrometer 10. Referring to FIG. 6, a plot 94 of ion intensity vs.drift time is shown illustrating the drift time of ions of the sodiatedmonomer [M+Na]⁺ form of the simple oligosaccharide isomer raffinosethrough one particular embodiment of the ion mobility spectrometer 10.In this embodiment, the drift time, DT, of raffinose through the drifttube 14 is approximately 15.8 ms.

Following step 82, the pulse width, PW, of the number of electric fieldactivation sources V₁-V_(M) used in the ion mobility spectrometerinstrument 10 is computed at step 84. The pulse width, PW, is theduration of the electric field that will be applied by each of theelectric field activation sources V₁-V_(M) to pass the sample componentof interest, e.g., raffinose, through each segment. In order to pass thesample component of interest through a drift tube 14 having N segments,the pulse width, PW, must therefore satisfy the relationship PW=DT/N.

Following step 84, the shape of the pulse width is selected at step 86,and thereafter at step 88 the peak voltage of the electric fieldactivation sources V₁-V_(M) is selected. The process 80 advances fromstep 88 to step 90, and simultaneously with step 90 the ion sourcevoltage supply, V_(IS), is controlled at step 92 in a manner that causesthe ion source 12 to produce ions. The ions produced at step 92 may beproduced continuously or may instead be produced discretely as describedhereinabove. In any case, the control circuit 18 is operable at step 90to control the electric field activation sources V₁-V_(M), as describedhereinabove, to sequentially apply electric fields having the selectedshape, duration and peak field strength to the various drift tubesegments, S₁-S_(N) as described hereinabove by example with reference toFIGS. 2-4D. Steps 90 and 92 may be repeated continuously or a finitenumber of times to thereby operate the ion mobility spectrometerinstrument 10 as a continuous or discrete ion mobility filter. For theraffinose sample illustrated in FIG. 6, the pulse width, PW, of theelectric field activation sources V₁-V_(M) in the ion mobilityspectrometer instrument 10 of FIG. 1, in which the drift tube 14 isconstructed of 20 drift tube segments, S₁-S₂₀, and one ion focusingfilter positioned approximately mid way between the ion inlet and ionoutlet of the drift tube 14, is approximately 500 microseconds, whichcorresponds to an electric field activation source switching frequencyof approximately 2.0 kHz. It will be understood that steps 82-88 are notrequired to be executed in the illustrated order, and that one or moreof these steps may alternatively be interchanged with one or more otherof these steps.

In addition to operation of the ion mobility spectrometer instrument 10as an ion mobility filter as illustrated and described herein, the ionmobility spectrometer instrument 10 may also be operated in a mannerthat transmits ions at overtone frequencies of the fundamentalfrequency, f_(f), as described briefly above. Referring to FIG. 7, forexample, a flowchart of an illustrative process 100 for operating theion mobility spectrometer 10 by sweeping the pulse widths, PW, of theelectric field activation sources, V₁-V_(M), over a range of pulse widthdurations. In addition to producing a fundamental ion intensity peakthat corresponds to ion intensity peak resulting from the process 80 ofFIG. 5, the process 100 further produces overtone ion intensity peaksthat may be analyzed in the frequency domain to reveal additionalcharacteristics of the sample component of interest. The process 100illustrated in FIG. 7 may be provided, in whole or in part, in the formof instructions that are stored in the memory unit 20 of the controlcircuit 18 and that are executable by the control circuit 18 to controlthe ion mobility spectrometer instrument 10 in accordance with theprocess 100.

The process 100 begins at step 102 where initial and final pulse widthdurations, PW_(I) and PW_(F) respectively, and a ramp rate, R (or stepsize), are selected. Illustratively, the initial pulse width duration,PW_(I), may be selected to be slightly longer than necessary to producethe fundamental ion intensity peak so that the resulting ion intensityvs. frequency spectrum begins approximately at the fundamental peak.Illustratively, the final pulse width duration, PW_(F), may be selectedto be a frequency beyond which no useful information is expected tooccur, or beyond which no ion intensity information is sought. In anycase, the ramp rate, R, and/or frequency step size between the initialand final pulse width durations, PW_(I) and PW_(F), will typically beselected to provide sufficient time at each pulse width duration toextract useful information from the ion mobility spectrometer instrument10. Such information can be of the form of ion collision cross sections,Ω, which can be derived from OMS measurements according to the followingequation:

${\Omega = {\frac{\left( {18\pi} \right)^{1/2}}{16}{\frac{ze}{\left( {k_{b}T} \right)^{1/2}}\left\lbrack {\frac{1}{m_{1}} + \frac{1}{m_{B}}} \right\rbrack}^{1/2}\frac{E\left\lbrack {{\varphi \left( {h - 1} \right)} + 1} \right\rbrack}{f\left( {d_{t} + d_{e}} \right)}\frac{760}{P}\frac{T}{273.2}\frac{1}{N}}},$

where ze is ion charge, k_(b) is Boltzmann's constant, P and Tcorrespond to the buffer gas pressure and temperature respectively, N isthe neutral number density, E is the electric field, f is the fieldapplication frequency, the quantity φ(h−1)+1 is the harmonic number orovertone number, m_(I) and m_(B) correspond to the mass of the ion andthe mass of the buffer gas, respectively, and all other variables havebeen defined herein.

Following step 102, the shape of the pulse width is selected at step104, and thereafter at step 106 the peak voltage of the electric fieldactivation sources V₁-V_(M) is selected. The process 100 advances fromstep 106 to step 108, and simultaneously with step 108 the ion sourcevoltage supply, V_(IS), is controlled at step 110 in a manner thatcauses the ion source 12 to produce ions. The ions produced at step 110may be produced continuously or may instead be produced discretely asdescribed hereinabove, although if produced discretely a timingmechanism will typically be required to trigger new supplies of ionscoincident with the changing of the pulse width durations. In any case,the control circuit 18 is operable at step 108 to control the electricfield activation sources V₁-V_(M), as described hereinabove, to applyelectric fields having the selected shape and peak field strength to thedrift tube segments, S₁-S_(N) while sweeping the pulse width duration,PW, between PW_(I) and PW_(F) at the selected ramp rate and/or stepsize. It will be understood that steps 102-106 are not required to beexecuted in the illustrated order, and that one or more of these stepsmay alternatively be interchanged with one or more other of these steps.

While not specifically illustrated in FIG. 7 as a step in the process100, ion detection signals produced by the ion detector 16 may beprocessed by the control circuit 18 and converted to the frequencydomain in a conventional manner for further analysis and/or observation.For the raffinose sample illustrated in FIG. 6, for example, sweepingthe pulse width, PW, of the electric field activation sources V₁-V₄ inthe ion mobility spectrometer instrument 10 of FIG. 1 betweenapproximately 10 milliseconds down to approximately 22 micro-secondsyields the ion intensity vs. frequency spectrum 112 illustrated in FIG.8. Illustratively, the 3^(rd) overtone produces the most highly resolvedion intensity peak.

Generally, the overtones produced by frequency sweeps of the typeillustrated in FIG. 8 will be defined, at least in part, by the phase(φ) of the ion mobility spectrometer 100. Referring to FIG. 9, forexample, a number of plots 120, 122, 124, 126 and 128 are shown offrequency spectrums of raffinose in which the phase, φ, of the ionmobility spectrometer 10 correspondingly increases. In all cases, theelectric field activation sources, V₁-V_(M) were configured to operateas described hereinabove with respect to FIGS. 2-4D. In the plot 120,φ=2, and the associated frequency spectrum includes an ion peak at thefundamental frequency, f_(f), and additional peaks at the third andfifth overtones. In the plot 122, φ=3, and the associated frequencyspectrum includes an ion peak at the fundamental frequency, f_(f), andadditional peaks at the fourth and seventh overtones. In the plots 124,126 and 128, φ=4, 5 and 6 respectively. The frequency spectrum 124includes an ion peak at the fundamental frequency, f_(f), and additionalpeaks at the fifth, ninth and thirteenth overtones, the frequencyspectrum 126 includes an ion peak at the fundamental frequency, f_(f),and additional peaks at the sixth, eleventh and sixteenth overtones, andthe frequency spectrum 128 includes an ion peak at the fundamentalfrequency, f_(f), and additional peaks at the seventh, thirteenth andnineteenth overtones. It should be noted that as the phase of the ionmobility spectrometer 10 is increased, secondary overtones increasingappear between the fundamental peak, f_(f), and the first expectedovertone. These secondary overtones correspond to intermediate harmonicfrequencies, i.e., those between the overtone frequencies, and may carryadditional ion information.

Generally, the overtones that should be expected to be observed inembodiments of the ion mobility spectrometer 10 operated with uniform,constant electric fields in the various drift tube segments, S₁-S_(N) asdescribed hereinabove, are given by the equation H=φ(h−1)+1, h=1, 2, 3,. . . , where H is a harmonic number, φ is the phase of the ion mobilityspectrometer 10, and h is an integer. Thus, for φ=2, H=1, 3, 5, 7, . . ., for φ=3, H=1, 4, 7, 10, . . . , for φ=4, H=1, 5, 9, 13, . . . , forφ=5, H=1, 6, 11, 16, . . . , and for φ=6, H=1, 7, 13, 19, . . . , etc.

The resolving power, R, of the ion mobility spectrometer instrument 10is defined by the equation R_(OMS)=f/Δf, where f is the frequency atwhich maximum ion intensity of transmitted and Δf is the width of thepeak at half maximum. Generally, it is observed that the resolvingpower, R, of the ion mobility spectrometer instrument 10 increases withincreasing overtone number, H. The resolving power, R, of the ionmobility spectrometer instrument 10 is also influenced by the totalnumber, N, of drift tube segments, S₁-S_(N), used. Referring to FIG. 10,for example, a number of plots 130 are shown illustrating the shapes offundamental-frequency, ion intensity peaks for a four-phase (φ=4) ionmobility spectrometer instrument 10 in which the total number of drifttube segments, N, is varied between 11 and 43 as indicated on the leftportion of FIG. 10. The plots 130 were generated from a sample of thesodiated monomer [M+Na]⁺ form of the simple oligosaccharide isomermelezitose using the ion mobility instrument 10 illustrated anddescribed herein. As illustrated in FIG. 10, whereas the peakintensities do not change significantly, the widths, Δf, of the peaks athalf maximum decrease as N increases. For example, Δf₁₁, correspondingto the width of the N=11 peak at half maximum, is approximately 1600 Hz,whereas Δf₄₃, corresponding to the width of the N=43 peak at halfmaximum, is approximately 345 Hz. The ratio f/Δf, and thus, R_(OMS),accordingly increases as the number, N, of drift tube segments S₁-S_(N)increases.

In a conventional ion mobility spectrometer; that is to say, an ionmobility spectrometer in which a single electric field is applied acrossthe length of the drift tube, the resolving power is generallyunderstood to follow the relationshipR_(IMS)=SQRTR[(E*e*L)/(16*k_(b)*T*In2)], where E is the applied electricfield, e is the elementary charge value, L is the length of the drifttube, k_(b) is Boltzmann's constant, and T is the temperature of thedrift tube.

In the ion mobility instruments 10 illustrated and described herein, theoverall resolving power, R_(OMS), is a function of R_(IMS) and is also afunction of the total number, n, of drift tube segments, S₁-S_(N), thephase number, φ, of the applied electric field and the harmonic number,m. Illustratively, R_(OMS) is given by the equations:

$R_{OMS} = \frac{1}{1 - {\left\lbrack {1 - \frac{C}{R_{IMS}}} \right\rbrack\left\lbrack \frac{{mn} - \left\lbrack {\varphi - 1 - \frac{l_{e}}{l_{t} + l_{e}}} \right\rbrack}{mn} \right\rbrack}}$or$R_{OMS} = \frac{1}{{\frac{C}{R_{IMS}}\left\lbrack {1 - \frac{\varphi - 1 - \frac{l_{e}}{l_{t} + l_{e}}}{mn}} \right\rbrack} + \frac{\varphi - 1 - \frac{l_{e}}{l_{t} + l_{e}}}{mn}}$

where C is a constant and all other variables have been defined herein.It should be noted that the resolving power, R_(OMS), generallyincreases with increasing n and also with increasing m, and theresolving power, R_(OMS), decreases with increasing φ. It should also benoted that in the limit of high R_(IMS), the first term in thedenominator of the foregoing equation approaches zero and the foregoingequation reduces to R_(OMS)=m*n/[φ−1−I_(e)/(I_(t)+I_(e))].

It can further be shown that the resolving power of any peak in an OMSdistribution can obtained by replacing the harmonic number, m, in theabove equation with (φq+1), and then by multiplying the entire equationby the quantity (φ/k+1), where k is an overtone series index havinglimits of 0 to φ−1, and q is an overtone peak index having limits of 0to infinity.

Referring now to FIG. 11, plots of ion intensity vs. frequency are shownto illustrate one implementation of the enhanced resolving power of theion mobility spectrometer 10 at overtone frequencies. The plots of FIG.11 are frequency-domain plots that were generated with a two-phase (φ=2)configuration of the ion mobility instrument 10. In the plots of FIG.11, only the overtone peaks 3 and 5 are shown along with the peak at thefundamental frequency, 1. The plot 140 represents a frequency-domainplot of raffinose, the plot 142 represents a frequency-domain plot ofthe sodiated monomer [M+Na]⁺ form of the simple oligosaccharide isomermelezitose, and the plot 144 represents a frequency-domain plot of a 3:1raffinose:melezitose mixture. The frequency spectrum of the plot 144illustrates that whereas the raffinose and melezitose areindistinguishable at the fundamental frequency, they are partiallyresolved at the third overtone, 146 ₁ and 146 ₂, and are fully resolvedat the fifth overtone, 148 ₁ and 148 ₂. The harmonic/overtone analysisdescribed in this disclosure, e.g., the pulse width duration sweepingprocess 100 illustrated in FIG. 7, may therefore be used to accuratelyidentify a sample component of interest, and/or to distinguish a samplecomponent of interest from another sample component.

The raffinose and melezitose mixture can alternatively be resolved at ornear their fundamental frequencies if allowed to drift along asufficiently long drift distance. This may be accomplished, for example,by employing the ion mobility spectrometer operating techniqueillustrated in FIG. 5 in an ion mobility spectrometer having a circularor so-called cyclotron geometry, as illustrated and described inco-pending PCT Publication No. WO 2008/028159 A2, filed Aug. 1, 2007,the disclosure of which has been incorporated herein by reference.Referring now to FIG. 12A, plots 150, 152 and 154 are shown of such anexperiment in which raffinose and melezitose were separated in acircular or cyclotron geometry ion mobility spectrometer 160 having acyclotron portion constructed such that the drift tube, made up ofcascaded ion transmission sections (d_(t)) and ion elimination sections(d_(e)) as illustrated and described hereinabove with respect to FIGS.2-4, defines a closed and continuous ion travel path.

Referring to FIG. 12B, one illustrative embodiment of such a cyclotronion mobility spectrometer 160 is shown. In the illustrated embodiment,the drift tube is made up of four conventional ion funnels, F2-F5 joinedat each end by curved drift tube segments D1-D4. Two of the curved drifttube segments D1 and D4 have Y-shaped geometries. In addition to formingone drift tube segment of the cyclotron portion of the drift tube, thesegment D1 selectively direct ions generated by an ion source, e.g., anelectrospray ion source, ESI, coupled to D1 via a funnel/gatearrangement, F1/G1, into the cyclotron portion via an ion entrance drifttube section. In addition to forming another drift tube segment of thecyclotron portion of the drift tube, the segment D4 selectively directsions via an ion exit drift tube segment from the cyclotron portion andthrough a cascaded funnel, F6, and drift tube segment, D5 to an iondetector, DET. It will be understood that the embodiment of thecyclotron ion mobility spectrometer 160 shown in FIG. 12B is merelyillustrative, and that the cyclotron portion of the spectrometer 160 mayalternatively include more or fewer drift tube segments than the eightsegments (D1-D4 and F2-F5) shown. It will further be understood thatwhile the ion entrance drift tube segment is shown coupled between theion source (ES1-F1/G1) and the drift tube segment D1, it mayalternatively be coupled to a different one of the drift tube segments.Likewise, while the ion exit drift tube segment is shown coupled betweenthe drift tube segment D4 and the funnel segment F6, it mayalternatively be coupled to a different one of the drift tube segments.Moreover, while the ion entrance and exit drift tube segments are showncoupled to different ones of the drift tube segments, they mayalternatively be coupled to a common one of the drift tube segments suchthat ions are admitted to and extracted from the same drift tubesegment. It will further be understood that more or fewer drift tubesegments and/or ion funnels may be positioned between the ion outlet ofthe ion exit drift tube segment of D4 and the ion detector, DET. In oneembodiment, for example, the ion detector, DET, may be coupled directlyto the ion outlet of the ion exit drift tube segment of D4, and in otherembodiments any number of drift tube segments and/or ion funnels may bepositioned between the ion exit drift tube segment of D4 and the iondetector, DET. In any case, the ion detector, DET, may be conventionaland is configured to detect ions exiting the ion drift tube segmentportion of D4 and produce corresponding ion detection signals. Thememory of the control circuit illustratively includes instructionsstored therein that are executable by the control circuit to process theion detection signals in a conventional manner to determine ion mobilityspectral information therefrom.

Although not specifically shown in FIG. 12B for ease of illustration andunderstanding, it will be understood that a number, M, of electric fieldactivation sources are connected to the various drift tube sections ofthe cyclotron ion mobility spectrometer 160, a voltage source, V_(IS),is connected to the ion source (ES1-F1/G1), a source of buffer gas isfluidly coupled to the drift tube, and a control circuit is electricallyconnected to one or more of the M electric field activation sources,voltage source, V_(IS) and ion detector, all as illustrated anddescribed herein with respect to FIGS. 1-4. The control circuit, asdescribed hereinabove, illustratively includes a memory havinginstructions stored therein that are executable by the control circuitto control operation of the cyclotron ion mobility spectrometer 160. Thevarious voltage sources and control circuitry, as illustrated anddescribed above, are thus omitted from FIG. 12B for brevity. The number,M, may be any positive integer greater than 2, and general operation ofthe number, M, of electric field activation sources is illustrated anddescribed herein with respect to FIGS. 1-4.

The ion source is illustrated in FIG. 12B as an electrospray ion sourcefluidly coupled to an ion funnel/gate, F1/G1, although the ion sourcemay alternatively be or include any conventional ion source that may becontrolled, via the voltage source, V_(IS), by the control circuitaccording to instructions stored in the memory that are executable bythe control circuit to selectively produce ions in a single, e.g.,one-shot, periodic, e.g., pulsed, and/or continuous fashion as is knownin the art. The ion gate, G1, of the ion source is illustrativelypositioned at an ion inlet of the ion entrance drift tube segment of D1such that the ion source is coupled to the inlet of the ion entrancedrift tube segment of D1, and an ion outlet of the ion entrance drifttube segment of D1 is coupled to the cyclotron portion of D1. The ionexit drift tube segment of D4 likewise has an ion inlet that is coupledto the cyclotron portion of D4, and an ion outlet coupled to the inletof the ion funnel F6.

The drift tube of the cyclotron ion mobility spectrometer 160illustrated in FIG. 12B is, like the embodiments illustrated in FIGS.1-4, partitioned into multiple cascaded drift tube segments D1-D4 andF2-F5. In one embodiment, each of the drift tube segments D1-D4 andF2-F5 has an ion inlet at one end and an ion outlet at an opposite end,and an ion elimination region is defined between the ion outlet and theion inlet of each adjacent drift tube segment as illustrated anddescribed hereinabove with respect to FIGS. 1-4. The ion outlet of alast one of the drift tube segments, e.g., F5, is coupled to the ioninlet of the first one of the drift tube segments, e.g., D1, such thatthe drift tube defines therein a closed and continuous ion travel pathwhich, in the illustrated embodiment, extends clockwise within D1-D4 andF2-F5. Illustratively, as just described, the ion elimination regionsmay be defined between the ion outlets and ion inlets of each of thedrift tube segments D1-D4 and F2-F5, such as illustrated in FIG. 2, andin this embodiment, each of D1-D4 and F2-F5 is an ion transmissionsection, d_(t), and the ion elimination regions, d_(e), are definedbetween adjacent ones of D1-D4 and F2-F5. In alternative embodiments,the lengths of the funnel sections F2-F5 may be made shorter than thelengths of the drift tube sections D1-D4, and in this embodiment, thedrift tube sections D1-D4 are the ion transmission sections, d_(t), andthe funnel sections F2-F5 are the ion elimination sections, d_(e). Inother alternative embodiments, the lengths of the drift tube sectionsD1-D4 may be made shorter than the lengths of the funnel sections F2-F5,and in this embodiment the funnel sections F2-F5 are the iontransmission sections, d_(t), and the drift tube sections D1-D4 are theion elimination sections.

An ion gate arrangement is positioned within the drift tube segment D4,and is configured to control ion travel through the cyclotron and ionexit drift tube portions of D4. The ion gate arrangement is generallyresponsive to one set of one or more ion gate signals produced by thecontrol circuit to direct ions moving through the drift tubes D1-D3 andF2-F5 through the cyclotron drift tube portion of D4 such that the ionsmay continue to travel around the cyclotron portion of the spectrometer160 defined by D1-D4 and F2-F5 while also blocking the ions fromentering the ion exit drift tube segment portion of D4 such that ionsmoving through the cyclotron drift tube segment portion of D4 cannotadvance to the ion detector, DET. The ion gate arrangement is alsogenerally responsive to another set of the one or more ion gate signalsproduced by the control circuit to direct ions moving through the drifttubes D1-D3 and F2-F5 through the ion exit drift tube segment portion ofD4 while also blocking ions from moving completely through the drifttube segment portion of D4 such that the ions travelling around thecyclotron portion of the spectrometer 160 defined by D1-D4 and F2-F5 donot advance completely through the drift tube segment portion of D4 andinstead advance through the ion exit drift tube segment portion of D4 tothe ion detector, DET. The ion gate arrangement is thus responsive tothe one set of one or more ion gate signals to direct ions travelingthrough the cyclotron portion of the spectrometer 160 to the next drifttube section, e.g., F5, in the cyclotron portion of the spectrometer160, and to the other set of one or more ion gate signals to extract theions traveling through the cyclotron portion of the spectrometer 160 bydirecting the ions through the ion exit drift tube section of D4 towardthe ion detector, DET. Illustratively, the ion mobility spectrometer 160includes one or more additional voltage sources electrically connectedto the ion gate arrangement, and the control circuit is thus generallyoperable to control the ion gate arrangement to direct ions movingthrough, and or blocking ions from moving through, the ion gatearrangement by controlling operation of such voltage sources in aconventional manner. The one or more additional voltage sources may beconventional voltage sources included within, or in addition to, thenumber, M, of electric field activation sources. Illustratively, thememory of the control circuit has instructions stored therein that areexecutable by the control circuit to control operation of the ion gatearrangement just described by controlling operation of the one or moreadditional voltage sources.

In the embodiment illustrated in FIG. 12B, the ion gate arrangement justdescribed is implemented in the form of two separate ion gates; G2 apositioned in, or at the ion inlet of, the ion exit drift tube segmentportion of D4, and G2 b positioned in the cyclotron drift tube segmentportion of D4. In this embodiment, the one set of the one or more iongate signals described above may include a first ion gate signal towhich the ion gate G2 b is responsive to allow ions to pass therethroughand a second ion gate signal to which the ion gate G2 a is responsive toblock ions from passing therethrough, and the other set of the one ormore ion gate signals described above may include a third ion gatesignal to which the ion gate G2 b is responsive to block ions frompassing therethrough and a fourth ion gate signal to which the ion gateG2 a is responsive to allow ions to pass therethrough. Those skilled inthe art will recognize that the ion gate arrangement may include more orfewer ion gates variously positioned relative to D4 and controllable bythe control circuit or other electronic controller to direct ionsthrough the cyclotron drift tube segment portion of D4 while blockingions from entering the ion exit drift tube segment portion of D4, and toalternatively direct ions through the ion exit drift tube segmentportion of D4 while blocking ions from traveling completely through thecyclotron drift tube segment portion of D4.

In the embodiment illustrated in FIG. 12B, ions are introduced into thecyclotron portion (e.g., D1-D4 and F2-F5) of the spectrometer 160 viacontrol of the gate, G1, such that ions enter the cyclotron portion viathe ion entrance drift tube segment portion of D1. With the ion gates G2a and G2 b set that G2 b allows ions to pass therethrough and G2 ablocks ions from passing therethrough, ions are then directed around thecyclotron portion of the spectrometer 160 via sequential pulses appliedby the number, M, of electric field activation sources to the variouscyclotron sections D1-D4 and F2-F5 which create sequential electricfields in the cyclotron sections D1-D4 and F2-F5 at a desired frequencyor pulse rate as described hereinabove with respect to FIG. 5 to therebycause only ions supplied by the ion source that have a predefined ionmobility or range of ion mobilities defined by the frequency or pulserate to travel through the cyclotron portion of the spectrometer 160.Ions may be so directed around the cyclotron portion of the spectrometer160 any number of times, and can then be extracted from the cyclotronportion of the spectrometer 160 by controlling the ion gate G2 b toblock ions from passing therethrough and controlling the ion gate G2 ato allow ions to pass therethrough to the ion detector, DET. The number,M, of electric field activation sources may include two or more sourcesas illustrated and described hereinabove with respect to FIGS. 1-4, andthe electric fields created within the various drift tube segments D1-D4and F2-F5 of the cyclotron portion of the spectrometer 160 by thenumber, M, of The electric field activation sources may be constant,linear, non-linear or have any desired shape or profile, also asdescribed hereinabove. Illustratively, the electric fields created in F6and D5 when extracting ions from the cyclotron portion of thespectrometer 160 are constant, although these fields may alternativelyalso be linear, non-linear or have any desired shape or profile.

Illustratively, the memory of the control circuit has instructionsstored therein that are executable by the control circuit to control theion source voltage source, V_(IS), to produce ions, to control the iongate arrangement to direct ions around the cyclotron portion of thespectrometer 160 while blocking ions from the ion detector, and tosequentially activate the number, M, of electric field activationsources for a predefined time duration while deactivating the remainingnumber, M, of electric field activation sources to thereby cause onlyions supplied by the ion source that have a predefined ion mobility orrange of ion mobilities defined by the predefined time duration, e.g.,the activation frequency or pulse rate of the number, M, of electricfield activation sources, to travel through the cyclotron portion of thespectrometer 160 and, after the ions have traveled around the cyclotronportion of the spectrometer 160 a selected number of times, to controlthe ion gate arrangement to draw ions moving through the cyclotronportion of the spectrometer 160 into the ion exit drift tube segment andtoward the ion detector. As described hereinabove, the mobility or rangeof mobilities of ions resulting from operation of the spectrometer 160as just described is/are resonant with a fundamental frequency, f_(f),of operation of the electric field activation sources, V₁-V_(M).Alternatively or additionally, as described hereinabove with respect toFIGS. 7-9, the instructions stored in the memory of the control circuitmay include instructions that are executable by the control circuit toconduct OMS analysis, as this term has been defined hereinabove, bycontrolling the ion source voltage source, V_(IS), and the number, M, ofelectric field activation sources to sweep the activation frequency orpulse rate of the number, M, of electric field activation sources over apredefined set of activation frequencies or pulse rates to thereby causeions within the drift tube that have ion mobilities resonant with one ormore overtones, e.g., harmonic frequencies, of operation of the electricfield activation sources, V₁-V_(M), and/or that have ion mobilitiesresonant with fundamental frequencies of the activation frequencies orpulse rates, i.e., activation times, of the electric field activationsources, V₁-V_(M), for each of the discrete activation frequencies orpulse rates over the predefined set of activation frequencies or pulserates, to travel through the spectrometer 160.

Referring again to FIG. 12 a, the plot 150 represents the raffinose, R,and melezitose, M, ion peaks after 1¾ cycles of ion travel through thecyclotron portion of the instrument 160. The plot 152 similarlyrepresents the raffinose, R, and melezitose, M, ion peaks after 3¾cycles, and the plot 154 represents the raffinose, R, and melezitose, M,ion peaks after 6¾ cycles. While 1¾ cycles is sufficient to isolate eachof the raffinose and melezitose ions, it is evident from FIG. 12 a thatthe two ion peaks separate further as the number of cycles increases.

Referring now to FIG. 14, a flowchart is shown illustrating a process250 for operating the ion mobility spectrometer 160 of FIG. 12B to firstpre-fill the cyclotron portion of the spectrometer 160 with ionsgenerated by the ion source, and to then operate the spectrometer 160 asdescribed herein to cause only ions supplied by the ion source that havea predefined ion mobility or range of ion mobilities defined by theactivation frequency or pulse rate of the number, M, of electric fieldactivation sources, to travel through the spectrometer 160 and/or tosweep the activation frequency or pulse rate of the number, M, ofelectric field activation sources over a predefined set of activationfrequencies or pulse rates to thereby cause ions within the drift tubethat have ion mobilities resonant with one or more overtone, e.g.,harmonic, frequencies of operation of the electric field activationsource, V₁-V_(M), and/or that have ion mobilities resonant withfundamental frequencies of the activation frequencies or pulse rates,i.e., activation times, of the electric field activation sources,V₁-V_(M), for each of the discrete activation frequencies or pulse ratesover the predefined set of activation frequencies or pulse rates, totravel through the spectrometer 160. This process provides for asignificant increase in sensitivity and resolution compared withoperating the ion mobility spectrometer 160 with single pulses orpackets of ions produced by the ion source as described above.Illustratively, the process 250 is stored in the memory 20 of thecontrol circuit 18 in the form of instructions that are executable bythe control circuit 18 to control operation of the ion mobilityspectrometer 160. The process 250 begins at step 252 where theoperational settings of the number, M, of electric field activationsources are defined, and a value of an integer, N, is set. Inembodiments in which the spectrometer 160 will be operated to produceions having a mobility or range of mobilities that is/are resonant withonly a fundamental frequency, f_(f), of operation of the electric fieldactivation sources, V₁-V_(M), step 252 may include, for example, thesteps 82-88 of the process 80 of FIG. 5. In other embodiments in whichthe spectrometer 160 will be operated to produce ions having ionmobilities resonant with one or more overtones, e.g., harmonicfrequencies, of operation of the electric field activation sources,V₁-V_(M), step 252 may include, for example, the steps 102-106 of theprocess 100 of FIG. 7. In any case, the value of the integer, N,corresponds to the number of times ions will travel around the cyclotronportion of the drift tube defined by the ion mobility spectrometer 160.

Following step 252, the process 250 advances to step 254 where thecontrol circuit 18 is operable to control the ion source, e.g.,ES1-F1/G1, to produce ions and to open the ion gate G1, and to controlthe ion gate arrangement to open the ion gate G2 b and close the iongage, G2 a. By opening the ion gate G1, ions generated by the ion sourcemay thus enter the ion entrance drift tube portion of the drift tubesegment D1. By opening the ion gate G2 b and closing the ion gage G2 a,the generated ions will be confined to the cyclotron portion of thedrift tube (D1-D4 and F2-F5) and will be blocked from advancing to theion detector, DET, as described hereinabove. Thereafter at step 256, thecontrol circuit 18 is operable to control the electric field activationsources, V₁-V_(M), to allow ions produced by the ion source to fill thecyclotron portion of the drift tube, e.g., D1-D4 and F2-F5. In oneembodiment, step 256 comprises controlling the electric field activationsources, V₁-V_(M), in a conventional manner to allow ions of differentmobilities to enter and advance through the cyclotron portion of thedrift tube D1-D4 and F2-F5, i.e., to pass all ions generated by the ionsource from each of the plurality of drift tube segments D1-D4 and F2-F5to the next. This may be done, for example, by simultaneously andidentically activating all of the electric field activation sources,V₁-V_(M), such that a continuous, constant electric field is establishedin all of the ion transmission sections, d_(t), and ion eliminationsections, d_(e), of each of the adjacent drift tube segments. Thoseskilled in the art will recognize other techniques for controlling thevarious electric field activation sources, V₁-V₂, such that ionsgenerated by the ion source may enter and fill the cyclotron portion ofthe drift tube D1-D4 and F2-F5, and such other techniques arecontemplated by this disclosure.

Following step 256, the process 250 advances to step 258 where thecontrol circuit 18 is operable to control the ion source to stopproducing ions and to close the ion gate G1 so that no new ions from theion source enter the cyclotron portion of the drift tube. Thereafter atstep 260, the control circuit 18 is operable to set a counter, L, equalto 1, and thereafter at step 262 the control circuit 18 is operable tocontrol the electric field activation sources, V₁-V_(M), to according tosource settings, e.g., those determined at step 252, to direct ions onerevolution around the cyclotron portion of the drift tube, i.e., onecomplete path about the closed cyclotron defined by D1-D4 and F2-F5.Illustratively, the control circuit 18 is operable at step 262 tocontrol the electric field activation sources, V₁-V_(M), by sequentiallyactivating, as described hereinabove with respect to FIG. 5, one or moreof the number, M, of electric field activation sources V₁-V_(M), for thetime duration, i.e., pulse width for activation of the sources V₁-V_(M)as determined at step 252, while deactivating the remaining number, M,of electric field activation sources to thereby cause only ions withinthe drift tube (D1-D4 and F2-F5) that have a predefined ion mobility orrange of ion mobilities defined by the time duration to travel throughthe drift tube. In this embodiment, ions having the predefined ionmobility or range of ion mobilities travel, under such control at step262, one revolution around the drift tube defined by D1-D4 and F2-F5.Thereafter at step 264, the control circuit 18 is operable to determinewhether the counter, L, is equal to the number N. If not, the process250 advances to step 266 where the counter, L, is incremented by 1 andthe process 250 then loops back to again execute step 262. If, at step264, the control circuit 18 determines that L=N, then the ions havetraveled around the cyclotron portion of the drift tube (D1-D4 andF2-F5) the selected number of times, N, and the process 250 advances tostep 268.

At step 268, the control circuit 18 is operable to control the ion gatearrangement to close the ion gate G2 b and open the ion gate G2 a, andto control the electric field activation sources, V₁-V_(M), thereafterat step 270 to sequentially direct ions in the cyclotron portion of thedrift tube to the ion detector, DET. With the ion gate G2 b closed andthe ion gate G2 a open, sequential operation of the electric fieldactivation sources V₁-V_(M) in the manner just described with respect tostep 262 is thus carried out at step 270, in addition to sequentiallyactivating electric fields within F6 and D5 in like manner, tosequentially direct the ions in the cyclotron portion of the drift tubethat have the predefined ion mobilities or range of ion mobilitiesthrough the ion exit drift tube segment of D4, through F6 and D5, and tothe ion detector, DET. Optionally, the process 250 may include an extrastep 272, executed following step 270, in which the control circuit 18is operable to execute steps 254-270 until the pulse width durations,i.e., the “time durations” of activations of the electric fieldactivation sources, V₁-V_(M), have been swept through a range of pulsewidth durations between an initial pulse width duration, PW, and a finalpulse width duration, PW_(F). In embodiments which include step 272,step 252 will of course include a determination of PW_(I) and PW_(F) asillustrated in the process 100 of FIG. 7. Generally, PW_(I) and PW_(F)will be selected to produce one or more overtones, i.e., harmonicfrequencies of which the predefined ion mobilities or range of ionmobilities are resonant, and/or to produce ions that have ion mobilitiesresonant with fundamental frequencies of the activation frequencies orpulse rates, i.e., activation times, of the electric field activationsources, V₁-V_(M), for each of the discrete activation frequencies orpulse rates over and between PW_(I) and PW_(F), as describedhereinabove.

Referring now to FIG. 15, a flowchart is shown illustrating anotherprocess 300 for operating the ion mobility spectrometer 160 of FIG. 12Bto selectively add ions from the ion source to the cyclotron portion ofthe spectrometer 160 during each of a first number of revolutions ofions around the cyclotron portion of the drift tube of the ion mobilityspectrometer 160 in which only ions that have a predefined ion mobilityor range of ion mobilities sequentially advance through the cyclotronportion of the drift tube, and to then stop adding ions and operate thespectrometer 160 as described herein to cause only ions in the cyclotronportion of the drift tube that have the predefined ion mobility or rangeof ion mobilities defined by the activation frequency or pulse rate ofthe number, M, of electric field activation sources, to travel aroundthe cyclotron portion of the drift tube a second number of times beforebeing directed to the ion detector. Optionally, this process may also bedone while also sweeping the activation frequency or pulse rate of thenumber, M, of electric field activation sources over a predefined set ofactivation frequencies or pulse rates to thereby cause ions within thedrift tube that have ion mobilities resonant with one or more overtone,e.g., harmonic, frequencies of operation of the electric fieldactivation source, V₁-V_(M), and/or to cause ions that have ionmobilities resonant with fundamental frequencies of the activationfrequencies or pulse rates, i.e., activation times, of the electricfield activation sources, V₁-V_(M), for each of a number of discreteactivation frequencies over the predefined set of activation frequenciesor pulse rates, to travel through the spectrometer 160. In any case, theprocess 300 is illustratively stored in the memory 20 of the controlcircuit 18 in the form of instructions that are executable by thecontrol circuit 18 to control operation of the ion mobility spectrometer160.

The process 300 begins at step 302 where the operational settings of thenumber, M, of electric field activation sources are defined, and valuesof two integers, N and M are set. In embodiments in which thespectrometer 160 will be operated to produce ions having a mobility orrange of mobilities that is/are resonant with only a fundamentalfrequency, f_(f), of operation of the electric field activation sourcesstep 252 may include, for example, the steps 82-88 of the process 80 ofFIG. 5. In other embodiments in which the spectrometer 160 will beoperated to produce ions having ion mobilities resonant with one or moreovertones, e.g., harmonic frequencies, of operation of the electricfield activation sources step 252 may include, for example, the steps102-106 of the process 100 of FIG. 7. In any case, the integer M set atstep 302 is different from, and should not be confused with, the number,M, of electric field activation sources.

Following step 302, the process 300 advances to step 304 where thecontrol circuit 18 is operable to control the ion source, e.g.,ES1-F1/G1, to produce ions and to control the ion gate arrangement toopen the ion gate G2 b and close the ion gate, G2 a. By opening the iongate G1, ions generated by the ion source may thus enter the ionentrance drift tube portion of the drift tube segment D1. By opening theion gate G2 b and closing the ion gate G2 a, ions introduced into thespectrometer 160 via the ion source will be confined to the cyclotronportion of the drift tube and will be blocked from advancing to the iondetector, DET, as described hereinabove. Thereafter at step 306, thecontrol circuit 18 is operable to set a counter, L, equal to 1.

Following step 306, the process 300 advances to step 308 where thecontrol circuit 18 is operable to control the ion source to open the iongate G1, and to control the electric field activation sources, V₁-V_(M),to according to source settings, e.g., those determined at step 302, toallow ions from the ion source to enter the first drift tube segment,e.g., D1, and to also advance ions already in the cyclotron portion ofthe drift tube to the next sequential drift tube segment(s). Thereafterat step 310, the control circuit 18 is operable to close the ion gateG1, and to control the electric field activation sources, V₁-V_(M),according to the source settings to advance ions in the cyclotronportion of the drift tube to the next sequential drift tube segment(s).Optionally, step 310 may also include controlling the ion source to stopproducing ions and step 308 may include controlling the ion source toproduce ions. In any case, following step 310 the process 300 advancesto step 312 where the control circuit 18 determines whether the counter,L, is equal to the sum of the integer M and another integer P. If not,the process advances to step 314 where the counter, L, is incremented by1 before again executing steps 308 and 310. If, at step 312, the controlcircuit 18 determines that L=M+P, the process 300 advances to step 316where the control circuit 18 controls the ion source to stop producingions and to reset the counter, L, equal to 1.

The sub-process of the process 300 between and including steps 302 and316 controls the ion mobility spectrometer 160 as described hereinaboveto sequentially advance only ions around the cyclotron portion of thedrift tube having ion mobilities or range of ion mobilities defined bythe activation pulse widths, i.e., time durations of activation, of theelectric field activation sources. During this process ions generated bythe ion source are also selectively added to the first drift tubesegment, D1, during and throughout a selected number, M, of revolutionsof the ions around the cyclotron portion of the drift tube (D1-D4 andF2-F5). This sub-process of the process 300 between and including steps302 and 316 may be referred to herein as “selective enhancement.” Theinteger P corresponds to the number of times steps 308 and 310 must beexecuted to sequentially fill and advance ions one revolution around thecyclotron portion of the drift tube, and the integer M corresponds tothe number of times steps 308 and 310 must be executed to continue theprocess of sequentially filling and advancing ions one revolution aroundthe cyclotron portion of the drift tube in order to direct the ionscompletely around the cyclotron portion of the drift tube a desirednumber of times while also selectively adding ions to the drift tube.The total number of revolutions, R, of the ions around the cyclotronportion of the drift tube when the “YES” branch of step 312 is satisfiedwill thus be M/P+1.

Referring now to FIGS. 16A-16L, the selective enhancement sub-process ofthe process 300 is graphically illustrated in the context of the variousdrift tube sections of the cyclotron ion mobility spectrometer 160 ofFIG. 12B. It will be understood that in FIGS. 16A-16L the ion mobilityspectrometer 160 is partitioned into eight cascaded drift tube segmentsD1-D4 and F2-F5 each having an ion transmission section, d_(t), and anion elimination region, d_(e), between the ion outlet of the iontransmission section and the ion inlet of the ion transmission sectionof the next adjacent segment. Thus, D1 has an ion elimination regionbetween the ion outlet of D1 and the ion inlet of F2, F2 has an ionelimination region between the ion outlet of F2 and the ion inlet of D2,etc. The ion elimination regions, d_(e), are not specifically shown inFIGS. 16A-16L, although it will be understood that electric fieldswithin these regions are established as described hereinabove withrespect to FIGS. 1-4 under control of the plurality of electric fieldactivation sources, V₁-V_(M). In alternative embodiments, as describedhereinabove, the drift tube segments D1-D4 may be sized to serve as theion transmission sections and the funnel segments F2-F5 may be sizedsmaller and serve as the ion elimination regions to D1-D4 respectively,or the funnel segments F2-F5 may be sized to serve as the iontransmission sections and the drift tube segments D1-D4 may be sizedsmaller and serve as the ion elimination regions to F2-F5 respectively.In any case, each sequential pair of FIGS. 16A-16L represent sequentialsnapshot of ions within the spectrometer 160 at the end of steps 308 and310 respectively. Thus, for example, FIG. 16A represents a snapshot ofions within the spectrometer 160 at the end of the first execution ofstep 308, FIG. 16B represents a snapshot of ions within the spectrometer160 at the end of the first execution of step 310, FIG. 16C represents asnapshot of ions within the spectrometer at the end of the secondexecution of step 308, etc.

Referring to FIG. 16A, the first execution of step 308 has occurred, anda group or packet of ions, 11, generated by the ion source 350 has movedthrough the ion inlet gate, G1, at the entrance of the ion entrancedrift tube segment of D1, and has moved under the influence of anelectric field established in the ion entrance drift tube segment of D1toward the ion outlet of the ion transmission segment of D1. In FIG.16B, the ion gate G1 has been closed, and the ion packet I1 has movedunder the influence of an electric field established in D1/F2 toward theion outlet of the ion transmission segment of F2.

In FIG. 16C, the ion packet I1 has moved under the influence of anelectric field established in F2/D2 toward the ion outlet of the iontransmission segment of D2. At the same time, the ion gate G1 has beenopened and another packet of ions, I2, generated by the ion source 350has moved through the ion entrance drift tube segment of D1, and hasmoved under the influence of an electric field established in the ionentrance drift tube segment of D1 toward the ion outlet of the iontransmission segment of D1. In FIG. 16D, the ion gate G1 has beenclosed, and the ion packet I1 has moved under the influence of anelectric field established in D2/F3 toward the ion outlet of the iontransmission segment of F3 and the ion packet I2 has moved under theinfluence of an electric field established in D1/F2 toward the ionoutlet of the ion transmission segment of F2.

In FIG. 16E, the ion packet I1 has moved under the influence of anelectric field established in F3/D3 toward the ion outlet of the iontransmission segment of D3, and the ion packet I2 has moved under theinfluence of an electric field established in F2/D2 toward the ionoutlet of the ion transmission segment of D2. At the same time, the iongate G1 has again been opened and another packet of ions, 13, generatedby the ion source 350 has moved through the ion entrance drift tubesegment of D1, and has moved under the influence of an electric fieldestablished in the ion entrance drift tube segment of D1 toward the ionoutlet of the ion transmission segment of D1. In FIG. 16F, the ion gateG1 has been closed, and the ion packet I1 has moved under the influenceof an electric field established in D3/F4 toward the ion outlet of theion transmission segment of F4, the ion packet I2 has moved under theinfluence of an electric field established in D2/F3 toward the ionoutlet of the ion transmission segment of F3, and the ion packet I3 hasmoved under the influence of an electric field established in D1/F2toward the ion outlet of the ion transmission segment of F2.

In FIG. 16G, the ion packet I1 has moved under the influence of anelectric field established in F4/D4 toward the ion outlet of the iontransmission segment of D4 (since G2 a is closed and G2 b is open), theion packet I2 has moved under the influence of an electric fieldestablished in F3/D3 toward the ion outlet of the ion transmissionsegment of D3 and the ion packet I3 has moved under the influence of anelectric field established in F2/D2 toward the ion outlet of the iontransmission segment of D2. At the same time, the ion gate G1 has againbeen opened and another packet of ions, 14, generated by the ion source350 has moved through the ion entrance drift tube segment of D1, and hasmoved under the influence of an electric field established in the ionentrance drift tube segment of D1 toward the ion outlet of the iontransmission segment of D1. In FIG. 16H, the ion gate G1 has beenclosed, and the ion packet I1 has moved under the influence of anelectric field established in D4/F5 toward the ion outlet of the iontransmission segment of F5, the ion packet I2 has moved under theinfluence of an electric field established in D3/F4 toward the ionoutlet of the ion transmission segment of F4, the ion packet I3 hasmoved under the influence of an electric field established in D2/F3toward the ion outlet of the ion transmission segment of F3 and the ionpacket I4 has moved under the influence of an electric field establishedin D1/F2 toward the ion outlet of the ion transmission segment of F2.

In FIG. 16I, the ion packet I1 has moved under the influence of anelectric field established in the cyclotron portion of F5/D1 toward theion outlet of the ion transmission segment of D1, the ion packet I2 hasmoved under the influence of an electric field established in F4/D4toward the ion outlet of the ion transmission segment of D4, the ionpacket I3 has moved under the influence of an electric field establishedin F3/D3 toward the ion outlet of the ion transmission segment of D3 andthe ion packet I4 has moved under the influence of an electric fieldestablished in F2/D2 toward the ion outlet of the ion transmissionsegment of D2. At the same time, the ion gate G1 has again been openedand another packet of ions, I5, generated by the ion source 350 hasmoved through the ion entrance drift tube segment of D1, and has movedunder the influence of an electric field established in the ion entrancedrift tube segment of D1 toward the ion outlet of the ion transmissionsegment of D1. It will be observed in FIG. 16I that as ion packets movefrom D2 to D1, the widths of the ion packets I4-I1 respectivelydecrease. This decrease in ion packet width is intended to represent afiltering of ions according to ion mobility (determined by activationpulse width of the electric field activation sources) such that fewerions are included in I1 than in I2, fewer ions are included in I2 thanin I3, etc. The ions in ion packet I1 are thus more highly resolved thanthose in I2, etc. because the illustrated ion mobility filtering processsequentially eliminates more ions having ion mobility or range of ionmobilities outside of that defined by the activation pulse width, i.e.,the time duration of activation, of the electric field activationsources, V₁-V_(M) as the ions sequentially move through the variousdrift tube segments of the cyclotron portion of the ion mobilityinstrument 160.

In FIG. 16J, the ion gate G1 has been closed, and the ion packets I1 andI5 have together moved under the influence of an electric fieldestablished in D1/F2 toward the ion outlet of the ion transmissionsegment of F2 such that ion packets I1 and I5 are now combined in F2.The ion packet I2 has also moved under the influence of an electricfield established in D4/F5 toward the ion outlet of the ion transmissionsegment of F5, the ion packet I3 has moved under the influence of anelectric field established in D3/F4 toward the ion outlet of the iontransmission segment of F4 and the ion packet I4 has moved under theinfluence of an electric field established in D2/F3 toward the ionoutlet of the ion transmission segment of F3.

In FIG. 16K, the ion packet I2 has moved under the influence of anelectric field established in the cyclotron portion of F5/D1 toward theion outlet of the ion transmission segment of D1, the ion packet I3 hasmoved under the influence of an electric field established in F4/D4toward the ion outlet of the ion transmission segment of D4, the ionpacket I4 has moved under the influence of an electric field establishedin F3/D3 toward the ion outlet of the ion transmission segment of D3 andthe combination of ion packets I1 and I5 have moved under the influenceof an electric field established in F2/D2 toward the ion outlet of theion transmission segment of D2. At the same time, the ion gate G1 hasagain been opened and another packet of ions, I6, generated by the ionsource 350 has moved through the ion entrance drift tube segment of D1,and has moved under the influence of an electric field established inthe ion entrance drift tube segment of D1 toward the ion outlet of theion transmission segment of D1. In FIG. 16L, the ion gate G1 has beenclosed, and the ion packets I2 and I6 have together moved under theinfluence of an electric field established in D1/F2 toward the ionoutlet of the ion transmission segment of F2 such that ion packets 12and 16 are now combined in F2. The ion packet I3 has also moved underthe influence of an electric field established in D4/F5 toward the ionoutlet of the ion transmission segment of F5, the ion packet I4 hasmoved under the influence of an electric field established in D3/F4toward the ion outlet of the ion transmission segment of F4 and thecombination of ion packets I1 and I5 has moved under the influence of anelectric field established in D2/F3 toward the ion outlet of the iontransmission segment of F3.

Referring again to FIG. 15, the sub-process carried out by steps 302-316of the process 300 and illustrated in FIGS. 16A-16L can be executed anynumber of times to selectively add ions to individual packets of ionscirculating through the various drift tube segments D1-D4 and F2-F5 ofthe ion mobility spectrometer 160. As illustrated in FIGS. 16A-16H, theloop defined by steps 308-314 is executed four times to complete onerevolution of ions around the cyclotron portion (D1-D4 and F2-F5) of theion mobility spectrometer 160. Thus, “P” at step 312 is equal to four inthe illustrated embodiment, and the counter value “M” is thereforeselected such that the total desired number of revolutions, R, of ionsaround the cyclotron portion of the ion mobility spectrometer 160 duringthe selective enhancement sub-process of steps 302-316, i.e., duringwhich ions from the ion source 350 are selectively added to ions alreadycirculating through the cyclotron portion of the spectrometer 160, mustsatisfy the relation R=M/P+1 as described above.

It will be understood that the ion mobility spectrometer 160 may becontrolled and operated using similar yet alternate techniques toperform the selective enhancement process just illustrated and describedwith respect to FIGS. 16A-16L. For example, the spectrometer 160 may bealternatively operated such that ions from the ion source 350 fill theD1 and F2 regions during one field application setting. Next the fieldswould switch such that ions from F2 would move into the D2 region whileions from the source 350 would be shut off. Application of the nextfield would see the transmission of the ions with resonant mobilitiesinto the F3 region. At the same time, ions from the ion source 350 wouldbe allowed to fill the D1 and F2 regions again. Completion of anothertwo field application periods would yield ions in the F4 and F3 regionswith a filling of the D1 and F2 regions. Yet another two applicationperiods would result in ions in the F5, F4, and F3 regions as well as afilling of the D1 and F2 regions. With the addition of two moreapplication periods the first ion packet would reach the F2 region againhaving completed a full cycle around the cyclotron portion of the drifttube (D1-D4 and F2-F5). During this time, ions from the source would beallowed into the D1 and F2 region combining with this ion packet.Another cycle would see the filtering of these added ions according toresonant mobilities. Ions could be added to each successive packet for adesired amount of time or a desired number of cycles around thecyclotron portion of the drift tube (D1-D4 and F2-F5). Alternativelystill, the process just described could be modified to move ions aroundthe cyclotron portion of the spectrometer 160 using longer iontransmission regions. For example, the spectrometer 160 may bealternatively operated such that ions from the ion source 350 fill theD1 and F2 regions during one field application setting. The ion sourcemay then be shut off and an electric field may be activated in theD1/F2/D2/F3 region to move ions into the D2/F3 region, etc. Ions maythus be moved through the cyclotron portion of the spectrometer 160 bypropagating two regions worth of ions around the cyclotron portion usingfewer field applications to complete each traversal of the cyclotronportion of the spectrometer 160.

As described hereinabove, the design of the cyclotron portion of thedrift can be altered from that described above such that the D regionscomprise the ion transmission regions, d_(t), and the F regions comprisethe ion elimination regions, d_(e), or such that the F regions comprisethe ion transmission regions, d_(t), and the D regions comprise the ionelimination regions, d_(e). Those skilled in the art will recognize thatthe selective enhancement sub-process just described comprising steps302-316 may be easily modified to be performed using such an alternatedesign of the cyclotron portion of the drift tube (D1-D4 and F2-F5), andthat any such modifications to steps 302-316 would be a mere mechanicalstep for a skilled artisan.

Referring again to FIG. 15, the process 300 advances from step 316 tosteps 318-326, and optional also to step 328. Steps 318-328 areidentical to steps 262-272 illustrated and described hereinabove withrespect to FIG. 14, in which the control circuit 18 is operable tocontrol the electric field activation sources, V₁-V_(M), and the iongates G2 a and G2 b to cause the ions within the cyclotron portion ofthe ion mobility spectrometer 160 to travel around the cyclotron drifttube “N” times prior to directing the ions to the ion detector, DET,where N may be any positive integer. Optionally, step 328 may beincluded to perform overtone analysis, as this process is describedabove, using the combination of the selective enhancement sub-processdescribed above followed by controlling the spectrometer 160 tocirculate the post-selectively enhanced ions in the cyclotron drift tubeN times prior to directing the ions toward the ion detector, DET.

Mixtures may alternatively be resolved over long distances in lineardrift tubes, e.g., of the type illustrated in FIGS. 1-4, at or neartheir fundamental frequencies by controlling the electric fieldactivation sources, V₁-V_(M), in a manner that directs ions back andforth between the ends of the drift tube. More specifically, ionsentering the ion inlet of the drift tube 14 are directed by the electricfield activation sources, V₁-V_(M), toward the ion outlet of the drifttube 14 by selectively controlling the activation times and pulse widthsof the electric field activation sources as described hereinabove withrespect to FIGS. 1-5. In this embodiment, prior to reaching the ionoutlet, e.g., at or near the last drift tube segment, the controlcircuit 18 may control the electric field activation sources, V₁-V_(M),to reverse the direction of the sequentially applied electric fields tothe cascaded drift tube segments such that the ions reverse directionand move linearly toward the ion inlet of the drift tube 14. As before,the duration of the pulse widths, PW, would determine the range of ionmobilities of the ions traversing the drift tube 14. In any case, thismay be repeated any number of times to allow the ions to drift anydesired distance. After drifting the desired distance, a gate at the ionoutlet of the drift tube 14 may be activated to allow the ions to exitthe ion outlet of the drift tube 14 and be detected by an ion detectorpositioned to detect ions exiting the drift tube.

Running the drift separation in a back and forth manner as justdescribed can be limited in that ions that limit resolving power, e.g.,those with slightly mismatched mobilities, may not eliminated as theymove back to their initial positions on all even passes (i.e., the2^(nd), 4^(th), 6^(th), etc. pass through the drift tube). Thislimitation may be overcome by, for example, randomizing positions of theions in the drift tube during each pass of ions from the first drifttube segment to the last and/or during each pass of ions from the lastdrift tube segment to the first.

Referring now to FIG. 17, one illustrative embodiment of an ion mobilityspectrometer 400 is shown having a linear drift tube 14′ that isconfigured to randomize ion positions during each such pass of ions. Thedrift tube 14′ is identical to the drift tube 14 illustrated anddescribed hereinabove with respect to FIGS. 1-4 except that aconventional ion trap 402 is positioned between two adjacent ones of thenumber, N, of cascaded drift tube segments, e.g., between the ion outletof the third ion elimination region, d_(e)(3) and the ion inlet of thefourth ion transmission region, d_(t)(4). All other features of thedrift tube 14′ are identical to the drift tube 14 illustrated anddescribed hereinabove, and all other components of the ion mobilityspectrometer 400 are identical to correspondingly numbered components ofthe ion mobility spectrometer 10 illustrated and described hereinabove.The primary purpose of the ion trap 402 in the spectrometer 400 is totrap ions of the desired mobility during each pass of ions from thefirst drift tube segment to the last and/or during each pass of ionsfrom the last drift tube segment to the first to thereby randomize thepositions of the ions during each such pass. In this regard, the memory20 of the processor 18 has, in this embodiment, instructions storedtherein that are executable by the processor 18 to control the ion trap,e.g., via a suitable voltage source or voltage sources, which may or maynot be, or be part of, one or more of the electric field activationsources, V₁-V_(M), to trap ions therein during each pass of ions fromthe first drift tube segment to the last and/or during each pass of ionsfrom the last drift tube segment to the first for a trap period selectedto allow ions trapped within the ion trap 402 to randomize theirpositions relative to the ion trap 402 and thereby randomize theirpositions relative to the drift tube 14′. During the trap period, ionswill thus randomize their positions, causing a greater mismatch intiming for a population of undesired ions, e.g., those with slightlyoff-resonance mobilities. This will lead to more effective eliminationof these undesired ions. It will be understood that the ion trap 402illustrated in FIG. 17 may be alternatively positioned anywhere alongits length, i.e., at either end or between any two adjacent drift tubesegments. Alternatively or additionally, the drift tube 14′ may includetwo or more such ion traps 402 positioned anywhere along its length. Inone specific embodiment, for example, one such ion trap 402 ispositioned at one end of the drift tube 14′ and another such ion trap402 is positioned at an opposite end of the drift tube 14′. In thisembodiment, the control circuit controls each ion trap to trap ionstherein during each pass of ions from one end of the drift tube tot theother.

Referring now to FIG. 18, the ion mobility spectrometer 10 of FIG. 1 isshown alternatively configured to randomize ion positions during eachsuch pass of ions. In particular, the instructions stored in the memory20 include, in the embodiment illustrated in FIG. 18, instructions thatare executable by the control circuit 18 to control the strengths, i.e.,i.e., the magnitudes, of the electric fields established by the electricfield activation sources, V₁-V_(M), in a number of adjacent drift tubesegments. More specifically, the electric fields in a number of adjacentdrift tube segments are progressively diminished to cause the ions torandomize their positions relative to the drift tube 14 by bunching upin one or more of the number of adjacent drift tube segments. In theembodiment illustrated in FIG. 18, for example, the control circuit 18is configured to control the electric field activation sources,V₁-V_(M), to cause the magnitudes of the electric fields E₁-E₄ in thefour adjacent drift tube segments at each end of the drift tube todiminish such that E₁>E₂>E₃>E₄. In alternative embodiments, the numberof adjacent drift tube segments in which the electric fields arediminished in magnitude may be more or fewer, may comprise any number ofsuch adjacent drift tube segments at either or both ends of the drifttube 14, or may comprise any number of such adjacent drift tube segmentsbetween the two ends of the drift tube 14.

The back-and-forth mobility separation in the segmented drift tube asjust describe with respect to FIGS. 17 and 18 may alternatively oradditionally be used for OMS modes of operation as described hereinabovewith respect to FIG. 7. This allows the use of overtone frequencies as ameans of mobility selection. Additionally, such a device couldincorporate ion trapping on either end to allow for selective enrichmentof a mobility region prior to mobility selection refinement with theback-and-forth cycling of ions. Here, ions from a continuous or pulsedsource can pass through a linear drift tube in either direction andthose with resonant frequencies can be trapped in an ion trap positionedin the drift tube. After selective filling for a predetermined timeperiod, i.e., as described hereinabove with respect to FIGS. 16A-16L,the ions would then be cycled back-and-forth through the linear drifttube a number of times to obtain greater resolution (isolation of ionsof a given mobility). Referring to FIG. 19, one illustrative embodimentof such an ion mobility spectrometer 500 is shown in which an ion trap502 is positioned at the end of the linear drift tube 14″, which isotherwise identical to the drift tube 14 of FIGS. 1-4. The remainingcomponents of the spectrometer 500 are likewise identical tolike-numbered components of the spectrometer 10 of FIGS. 1-4 except thatthe memory includes instructions stored therein that are executable bythe control circuit 18 to control and operate the spectrometer 500 toselectively fill the drift tube 14″ for a predefined time period ornumber of back and forth cycles, and to thereafter cycle the ions backand forth a desired number of times as generally described hereinabovewith respect to FIGS. 15-16L.

Referring now to FIG. 20, a flowchart is shown of one illustrativeembodiment of a process 600 for operating the linear drift tube 14″ ofFIG. 19 as just described. Illustratively, the process 600 is stored inthe memory 20 of the control circuit 18 in the form of instructions thatare executable by the processor 18 to control operation of thespectrometer 500. The process 600 begins at step 602 where theoperational settings of the number, M, of electric field activationsources are defined, and a value of an integer, N, (and optionally M) isset. In embodiments in which the spectrometer 500 will be operated toproduce ions having a mobility or range of mobilities that is/areresonant with only a fundamental frequency, f_(f), of operation of theelectric field activation sources, V₁-V_(M), step 602 may include, forexample, the steps 82-88 of the process 80 of FIG. 5. In otherembodiments in which the spectrometer 500 will be operated to produceions having ion mobilities resonant with one or more overtones, e.g.,harmonic frequencies, of operation of the electric field activationsources, V₁-V_(M), step 602 may include, for example, the steps 102-106of the process 100 of FIG. 7.

Following step 602, the process 600 advances to step 604 where thecontrol circuit 18 is operable in one embodiment to reset a timer, e.g.,set a timer value, T, to zero (or to another arbitrary value), and in analternate embodiment to set a counter value, K, equal to 1. Thereafterat step 606, the control circuit 18 is operable to control the ionsource 12 to generate ions, and thereafter at step 608 the controlcircuit 18 is operable to control the electric field activation sources,V₁-V_(M), according to the source settings determined at step 602 tosequentially advance ions sequentially through the drift tube segmentstoward the last drift tube segment, i.e., toward the ion trap 502. Theions advance through the drift tube at step 608 will, of course, haveion mobilities or ranges of ion mobilities that are resonant with theactivation time, i.e., time duration of activation, of the electricfield activation sources V₁-V_(M) as illustrated and describedhereinabove. Thereafter at step 610, the control circuit 18 is operableto control the ion trap 502 to trap ions advanced through the drift tube14″ to the ion trap 502. Thereafter at step 612, the control circuit 18is operable to determine whether the timer has reached a predefined timeperiod, T_(P), since being reset, or to determine whether the value ofthe counter, K, has reached the value M which was optionally set at step602. In some embodiments, the ion source 12 is controlled at step 606 tocontinuously generate ions, and in other embodiments the ion source 12is controlled at step 606 to generate discrete packets or pulses ofions. In either case, a timer or a counter may be used to control theamount of time that ions are collected in the ion trap 502 or the numberof passes in which ions are advanced into the ion trap via the drifttube 14″. If a timer is used, step 612 loops back to step 606 (or tostep 608 in the case of continuous generation of ions) until T>T_(P). Ifa counter is used, step 612 advances to step 614 to increment K, and tothen loop back to step 606 (or to step 608 in the case of continuousgeneration of ions) until K=M, where M=the number of times ions areadvanced through the drift tube 14″ into the ion trap 502. In eithercase, the “YES” branch of step 612 advances to step 616 where thecontrol circuit 18 is operable to stop producing ions and to set acounter value, L, equal to 1.

Following step 616, the process 600 advances to step 618 where thecontrol circuit 18 controls the ion trap 502 and the electric fieldactivation sources, V₁-V_(M), to according to source settings, e.g.,those determined at step 602, to sequentially advance ions in the iontrap 502 in a reverse direction toward the first drift segment of thedrift tube 14″, i.e., to the d_(t)(1). When the ions are determined atstep 620 by the control circuit 18 to be in the first drift tube segment(e.g., as a function of time after being released from the ion trap 502at step 618), the process advances to step 622, and otherwise loops backto step 618 until step 620 is satisfied. At step 622, the controlcircuit 18 controls the electric field activation sources, V₁-V_(M), toaccording to source settings, e.g., those determined at step 602, tosequentially advance ions in the ion trap 502 in a forward directionfrom the first drift tube segment, d_(t)(1) toward last drift tubesegment, i.e., the ion trap 502. Thereafter at step 624, the controlcircuit 18 is operable to control the ion trap 502 to trap therein ionspassing through the last drift tube segment for a time period, T_(T),where T_(T) is a trapping time period that allows the ions to randomizeas described hereinabove with respect to FIG. 17. Thereafter at step626, the control circuit 18 is operable to determine whether thecounter, L, is equal to the number N. If not, the process 600 advancesto step 628 where the counter, L, is incremented by 1 and the process600 then loops back to again execute step 618. If, at step 626, thecontrol circuit 18 determines that L=N, then the ions have traversed thelinear drift tube 14″ the desired number of times, and the process 600advances to step 630 where the control circuit 18 is operable to controlthe ion trap 502 to direct ions trapped therein to the ion detector 16.Optionally, the process 600 may include an extra step 632, executedfollowing step 630, in which the control circuit 18 is operable toexecute steps 604-630 until the pulse width durations, i.e., the “timedurations” of activations of the electric field activation sources,V₁-V_(M), have been swept through a range of pulse width durationsbetween an initial pulse width duration, PW_(I) and a final pulse widthduration, PW_(F). In embodiments which include step 632, step 602 willof course include a determination of PW_(I) and PW_(F) as illustrated inthe process 100 of FIG. 7. Generally, PW_(I) and PW_(F) will be selectedto produce one or more overtones, i.e., harmonic frequencies of whichthe predefined ion mobilities or range of ion mobilities are resonant,and/or to produce ions that have ion mobilities resonant withfundamental frequencies of the activation frequencies or pulse rates,i.e., activation times, of the electric field activation sources,V₁-V_(M), for each of the discrete activation frequencies or pulse ratesover and between PW_(I) and PW_(F), as described hereinabove.

While the spectrometer 500 illustrated in FIG. 19 is illustrated withthe ion trap 502 located at one end of the drift tube 14″, it will beunderstood that the ion trap 502 may alternatively be positioned at theopposite end of the drift tube 14″ or between the two ends of the drifttube 14″. Alternatively or additionally, any number of ion traps may bepositioned in the drift tube 14″, e.g., one at each end, for the purposeof trapping and randomizing positions of the ions trapped therein asillustrated and described with respect to FIG. 17, and/or the magnitudesof the electric fields of a number of adjacent ones of the drift tubesegments may be sequentially diminished to enhance or achieve thisresult as illustrated and described with respect to FIG. 18. In suchcase or cases, the ion trap 502 may, need not, be controlled in asdescribed for the purpose of randomizing ions trapped therein.

In any of the linear or cyclotron configurations of the ion mobilityspectrometer illustrated and described herein, a non-destructivedetector, e.g., rather than an ion counting detector 16, could be usedthat is configured to measure the image charge many times at a specifiedposition within drift tube. Ion distributions could then be recorded asthe frequency that ions pass the non-destructive detector. Aconventional frequency transformation, e.g., Fourier transform, couldthen be used to back-calculate ion mobility.

Referring now to FIG. 21, yet another embodiment of an ion mobilityspectrometer 600 is shown. In the illustrated embodiment, some of theillustrated components are identical to those described hereinabove, andlike reference numbers are therefore used to identify like components.In FIG. 21, the drift tube 602 includes a single drift tube segment oflength L positioned between two ion traps 604 and 606. The ion trap 604is positioned adjacent to the inlet of the single drift tube segment602, and the ion trap 606 is positioned adjacent to the ion outlet ofthe single drift tube segment 602. At least one drift tube voltagesource, V_(DT), is electrically connected between the control circuit 18and the single drift tube segment 602, and is controllable in aconventional manner to establish an electric field in the single drifttube region 602 in one direction that causes ions supplied by the ionsource 12 to drift from the ion trap 604 toward the ion trap 606, and toalternatively establish an electric drift field in the single drift tuberegion 602 in an opposite direction that causes ions to drift from theion trap 606 toward the ion trap 604. An ion trap voltage source,V_(IT1), is electrically connected between the control circuit 18 andthe ion trap 604, and another ion trap voltage source, V_(IT2), iselectrically connected between the control circuit 18 and the ion trap606.

The memory 20 illustratively includes instructions stored therein thatare executable by the control circuit 18 to execute a process apredefined number of times. The process illustratively includesactivating the at least one electric field activation source, V_(DT),for a time duration to establish an electric field in the one directionto cause only ions supplied by the ion source 12 that have a predefinedion mobility or range of ion mobilities defined by the time duration totravel through the single drift tube region 602 in the direction fromthe ion trap 604 toward the second ion trap 606 followed by controllingthe ion trap 606 to trap therein the ions that have the predefined ionmobility or range of ion mobilities. The ion trap 606 is then controlledto release the ions trapped therein and the control circuit 18 thenactivates the at least one electric field activation source, V_(DT), forthe time duration to establish an electric field in the oppositedirection to cause only ions that have the predefined ion mobility orrange of ion mobilities defined by the time duration to travel throughthe single drift tube region 602 in the direction from the ion trap 606toward the ion trap 604 followed by controlling the ion trap 604 to traptherein the ions that have the predefined ion mobility or range of ionmobilities followed by controlling the ion trap 604 to release the ionstrapped therein. This process may be performed any number of times tothereby cause ions to traverse the single drift tube region 602 any suchnumber of times. The control circuit 18 may then control the ion trap606 to release ions trapped therein toward the ion detector 16 and toprocess the ion detection signals produced by the ion detector todetermine ion mobility spectral information therefrom. The ion source 12may be controlled in a pulsed fashion to produce discrete packets ofions or may alternatively be controlled to continuously produce ions.The instructions stored in the memory 20 may further includeinstructions executable by the control circuit 18 to control the iontraps 604 and 606 to trap ions therein for a trap period. The trapperiod is illustratively selected to allow ions trapped within the iontrap 604 and within the ion trap 606 to randomize their positionsrelative to the respective ion trap 604/606.

The spectrometer 600 may alternatively be operated in the OMS modeillustrated and described hereinabove. For example, the instructionsstored in the memory 20 may further include instructions executable bythe control circuit 18 to control the at least one electric fieldactivation source, V_(DT), to sweep the time duration between first andsecond predefined time durations to thereby cause ions that havefundamental frequencies resonant with each of a number of discrete timedurations between the first and second time durations to travel throughthe single drift tube region 602, and to execute the process thepredefined number of times for each of the number of discrete timedurations between the first and second predefined time durations.

Referring now to FIG. 13, a block diagram of one illustrative embodimentof a cascaded ion mobility spectrometer instrument 170 is shown thatemploys some of the concepts illustrated and described hereinabove withrespect to FIGS. 1-12B. In the illustrated embodiment, the instrument170 includes an ion source 12 having an ion outlet coupled to an ioninlet of a first ion mobility spectrometer (IMS1). An ion outlet of IMS1is coupled to an ion inlet of a second ion mobility spectrometer (IMS2)having an ion outlet that is coupled to an ion detector 16. The IMS1 hasan axial length of L1 and the IMS2 has an axial length of L2. A controlcircuit 180 includes a memory unit 182, and is electrically connected toa control input of an ion source voltage supply, V_(IS), having anoutput that is electrically connected to the ion source 12. Theinstrument 170 further includes a plurality of electric field activationsources, V₁-V_(Q), that are electrically connected between the controlcircuit 180 and IMS1 and IMS2, where Q may be any integer greaterthan 1. Illustratively, a subset of the electric field activationsources, V₁-V_(p), are dedicated to IMS1, and another subset,V_(P+1)-V_(Q) are dedicated to IMS2. Alternatively, V_(P+1)-V_(Q) may beomitted, and V₁-V_(P) may be used for both of IMS1 and IMS2. In anycase, each of the foregoing components may be as described hereinabovewith respect to the embodiment of FIG. 1. In one illustrativeembodiment, the instrument 170 is operable just as described hereinabovewith respect to any of FIGS. 1-12B, except that the ions are resolvedover an effective drift tube length of L1+L2 rather than over the lengthof a single drift tube, such that IMS1 and IMS2 together form a singleion mobility spectrometer.

The ion mobility spectrometer instrument 170 of FIG. 13 may furtherinclude at least one additional voltage source, V_(F), which may becontrolled by the control circuit 180 to produce one or more voltagesthat control one or more ion fragmentation units or other conventionaldevice for inducing structural changes in ions within IMS1, IMS2 and/orpositioned between IMS1 and IMS2. In embodiments in which the drifttubes of IMS1 and IMS2 are constructed according to the teachings ofco-pending U.S. Patent Application Pub. No. US 2007/0114382, forexample, an ion activation region of the type described therein may bepositioned at the end of any one or more ion funnels that form IMS1and/or IMS2. Alternatively, IMS1 and/or IMS2 may be modified in otherembodiments to include one or more conventional structural changeinducing devices or stages, e.g., one or more ion fragmentation stages,ion conformational change stages, and/or other conventional structuralchange inducing devices or stages, therein or interposed between IMS1and IMS2. For example, such a structural change inducing device may bepositioned between IMS1 and IMS2, and the ion mobility spectrometer 170may be operated as described hereinabove to conduct fundamentalfrequency and/or overtone frequency analysis with IMS1, to then inducestructural changes in ions emerging from IMS1, and to then conductfundamental frequency and/or overtone frequency analysis with IMS2 onthe ions in which structural changes were induced. Alternatively oradditionally, the fragmented ions may be mobility filtered in aconventional manner prior to entering IMS2. Alternatively oradditionally still, such fragmented and mobility-selected ions may befurther fragmented and possibly further mobility selected any number oftimes prior to entrance into IMS2.

IMS1 may further include an operating condition selection unit 190, andIMS2 may likewise include an operating condition selection unit 200. Theoperating condition selection units 190 and 200 may be manuallycontrolled via respective manual controls 194 and 204, and/or may beautomatically controlled by the control circuit 180 via suitableelectrical control lines 192 and 202 respectively. The operatingcondition selection units 190 and 200 are block diagram components thatmay represent conventional structures that control any one or more ofthe operating temperature of IMS1 and/or IMS2, the operating pressure ofIMS1 and/or IMS2, the chemical make up and/or flow rate of gas, e.g.,buffer gas, supplied to the ion pathway of IMS1 and/or IMS2, and thelike. In the operation of the ion mobility spectrometer instrument 170,such as described hereinabove, IMS1 and IMS2 may be operated asdescribed hereinabove and further with any one or more of, or with anycombination of, the same or different drift tube lengths, L1 and L2, thesame or different electrical field strengths applied by the electricfield activation sources V₁-V_(Q), the same or different pulse shapesapplied by the electric field activation sources V₁-V_(Q), the same ordifferent pulse width durations, PW, applied by the electric fieldactivation sources V₁-V_(Q), the same or different operatingtemperatures (e.g., T1 for IMS1 and T2 for IMS2), the same or differentoperating pressures, (e.g., P1 for IMS1 and P2 for IMS2), with the ionspassing through IMS1 and IMS2 exposed to the same or different gasses(Gas1 for IMS1 and Gas2 for IMS2), or with ion fragmentation occurringwithin or between IMS1 and IMS2. Further details relating to some ofthese operational scenarios or modes are provided in U.S. Pat. No.7,077,904, the disclosure of which is incorporated herein by reference.

It will be understood that the ion mobility spectrometer instrumentillustrated in FIG. 13 and described herein represents only an examplemultiple drift tube instrument, and that the instrument mayalternatively include any number of IMS units or drift tubes.Alternatively still, the IMS drift tubes in such an arrangement need notbe linear, and the instrument 170 illustrated in FIG. 13 may include anynumber of non-linear IMS drift tube, such as two or more circular drifttubes of the type described in co-pending PCT Publication No. WO2008/028159 A2, filed Aug. 1, 2007, the disclosure of which has beenincorporated herein by reference.

While the invention has been illustrated and described in detail in theforegoing drawings and description, the same is to be considered asillustrative and not restrictive in character, it being understood thatonly illustrative embodiments thereof have been shown and described andthat all changes and modifications that come within the spirit of theinvention are desired to be protected.

1. An ion mobility spectrometer instrument comprising: a drift tubepartitioned into a plurality of cascaded drift tube segments, eachdefining an ion inlet at one end and an ion outlet at an opposite end,with an ion elimination region defined between the ion outlet and an ioninlet of each adjacent drift tube segment, the ion elimination region ofa last one of the drift tube segments coupled to the ion inlet of afirst one of the drift tube segments such that the drift tube definestherein a closed and continuous ion travel path, an ion source, an ionentrance drift tube segment having an ion inlet coupled to the ionsource and an ion outlet coupled to one of the plurality of cascadeddrift tube segments, an ion exit drift tube segment having an ion inletcoupled to the one or another one of the plurality of drift tubesegments, and an ion outlet, an ion gate arrangement responsive to afirst set of one or more ion gate signals to direct ions moving throughthe drift tube through the one or another one of the plurality ofcascaded drift tube segments while blocking the ions from entering theion exit drift tube segment, and to a second set of one or more ion gatesignals to direct the ions moving through the drift tube into the ionexit drift tube segment while blocking the ions from moving through theone or another one of the plurality of cascaded drift tube segments, anumber, M, of electric field activation sources each operativelyconnected to one or more of the plurality of drift tube segments suchthat, when activated, each establishes a repulsive electric field in atleast one of the first M ion elimination regions and in every followingMth ion elimination region, and also establishes an electric drift fieldin all remaining ion elimination regions and in all of the plurality ofcascaded drift tube segments, and a control circuit including a memoryhaving instructions stored therein that are executable by the controlcircuit to produce the first set of one or more ion gate signals andsequentially activate each of the number, M, of electric fieldactivation sources for a time duration while deactivating the remainingnumber, M, of electric field activation sources to thereby cause onlyions supplied by the ion source that have a predefined ion mobility orrange of ion mobilities defined by the time duration to travel throughthe drift tube, and after the ions have traveled around the drift tube aselected number of times to produce the second set of one or more iongate signals to draw ions moving through the drift tube out of the drifttube and into the ion exit drift tube segment.
 2. The ion mobilityspectrometer of claim 1 further comprising an ion detector configured todetect ions exiting the ion exit drift tube segment and producecorresponding ion detection signals, wherein the instructions stored inthe memory further include instructions executable by the controlcircuit to process the ion detection signals to determine ion mobilityspectral information therefrom.
 3. The ion mobility spectrometer ofclaim 1 wherein the ion gate arrangement comprises: a first ion gatepositioned in the one or another one of the plurality of cascaded drifttube segments, and a second ion gate positioned in or at the ion inletof the ion exit drift tube segment, wherein the first set of one or moreion gate signals comprises a first ion gate signal to which the firstion gate is responsive to allow ions to pass therethrough and a secondion gate signal to which the second ion gate is responsive to block ionsfrom passing therethrough, and wherein the second set of one or more iongate signals comprises a third ion gate signal to which the first iongate is responsive to block ions from passing therethrough and a fourthion gate signal to which the second ion gate is responsive to allow ionsto pass therethrough.
 4. The ion mobility spectrometer of claim 1further comprising a voltage supply operatively connected to the ionsource and to the control circuit, wherein the instructions stored inthe memory further include instructions executable by the controlcircuit to control the voltage source to thereby selectively cause theion source to produce ions and to selectively supply produced ions tothe ion entrance drift tube segment.
 5. The ion mobility spectrometer ofclaim 1 wherein the instructions stored in the memory further includeinstructions executable by the control circuit to produce the first setof one or more ion gate signals, to control the ion source to produceions and control the number, M, of electric field activation sources ina manner that allows ions produced by the ion source to enter and filleach of the plurality of drift tube segments, to then control the ionsource to stop producing ions and sequentially activate each of thenumber, M, of electric field activation sources for the time durationwhile deactivating the remaining number, M, of electric field activationsources to thereby cause only ions within the drift tube that have thepredefined ion mobility or range of ion mobilities defined by the timeduration to travel through the drift tube, and after the ions havetraveled around the drift tube a selected number of times to produce thesecond set of one or more ion gate signals and control the number, M, ofelectric field activation sources to draw ions moving through the drifttube out of the drift tube and into the ion exit drift tube segment. 6.The ion mobility spectrometer of claim 5 wherein the instructions storedin the memory further include instructions executable by the controlcircuit to control the number, M, of electric field activation sourcesin the manner that allows ions produced by the ion source to enter andfill each of the plurality of drift tube segments by controlling thenumber, M, of electric field activation sources to pass all ionsgenerated by the ion source from each of the plurality of drift tubesegments to the next adjacent drift tube segment.
 7. The ion mobilityspectrometer of claim 5 wherein the predefined ion mobility or range ofion mobilities is resonant with a fundamental frequency defined by thetime duration, and wherein the instructions stored in the memory furtherinclude instructions executable by the control circuit to control thenumber, M, of electric field activation sources to sweep the timeduration between first and second predefined time durations to therebycause ions within the drift tube that have at least one of ionmobilities defined by overtone frequencies of the time duration and ionmobilities resonant with fundamental frequencies of discrete timedurations between the first and second time durations to travel throughthe drift tube.
 8. The ion mobility spectrometer of claim 5 furthercomprising a voltage supply operatively connected to the ion source andto the control circuit, wherein the instructions stored in the memoryfurther include instructions executable by the control circuit tocontrol the ion source to produce ions by controlling the voltage sourceto cause the ion source to produce ions and to supply the produced ionsto the ion entrance drift tube segment, and to control the ion source tostop producing ions by controlling the voltage source to cause the ionsource to stop producing ions.
 9. The ion mobility spectrometer of claim5 wherein the ion gate arrangement comprises: a first ion gatepositioned in the one or another one of the plurality of cascaded drifttube segments, and a second ion gate positioned in or at the ion inletof the ion exit drift tube segment, wherein the first set of one or moreion gate signals comprises a first ion gate signal to which the firstion gate is responsive to allow ions to pass therethrough and a secondion gate signal to which the second ion gate is responsive to block ionsfrom passing therethrough, and wherein the second set of one or more iongate signals comprises a third ion gate signal to which the first iongate is responsive to block ions from passing therethrough and a fourthion gate signal to which the second ion gate is responsive to allow ionsto pass therethrough.
 10. The ion mobility spectrometer of claim 5further comprising an ion detector configured to detect ions exiting theion exit drift tube segment and produce corresponding ion detectionsignals, wherein the instructions stored in the memory further includeinstructions executable by the control circuit to process the iondetection signals to determine ion mobility spectral informationtherefrom.
 11. The ion mobility spectrometer of claim 1 wherein the ionoutlet of the ion entrance drift tube segment is coupled to a first oneof the plurality of drift tube segments, and wherein the instructionsstored in the memory further include instructions executable by thecontrol circuit to produce the first set of the one or more gatesignals, and to then control the ion source and the number, M, ofelectric field activation sources to alternately (a) supply ions to thefirst one of the plurality of cascaded drift tube segments via the ionentrance drift tube segment while also advancing ions in even-numberedones of the plurality of drift tube segments to next adjacentodd-numbered ones of the plurality of drift tube segments and blockingadvancement of ions in odd-numbered ones of the plurality of drift tubesegments to next adjacent even-numbered ones of the plurality of drifttube segments, and (b) stop the supply of ions to the first one of theplurality of cascaded drift tube segments via the ion entrance drifttube segment while also advancing ions in odd-numbered ones of theplurality of drift tube segments to next adjacent even-numbered ones ofthe plurality of drift tube segments and blocking advancement of ions ineven-numbered ones of the plurality of drift tube segments to nextadjacent odd-numbered ones of the plurality of drift tube segments, afirst number of times to thereby sequentially add ions selectivelyproduced by the ion source to every other one of the plurality of drifttube segments.
 12. The ion mobility spectrometer of claim 11 wherein theinstructions stored in the memory further include instructions that areexecutable by the control circuit to, after ions selectively produced bythe ion source have been added to every other one of the plurality ofdrift tube segments the first number of times, control the ion source tostop producing ions and sequentially activate each of the number, M, ofelectric field activation sources for the time duration whiledeactivating the remaining number, M, of electric field activationsources to thereby cause only ions within the drift tube that have thepredefined ion mobility or range of ion mobilities defined by the timeduration to travel through the drift tube, and after the ions havetraveled around the drift tube a second number of times to produce thesecond set of the one or more ion gate signals to draw ions movingthrough the drift tube out of the drift tube and into the ion exit drifttube segment.
 13. The ion mobility spectrometer of claim 12 furthercomprising a voltage supply operatively connected to the ion source andto the control circuit, wherein the instructions stored in the memoryfurther include instructions executable by the control circuit tocontrol the ion source to produce ions by controlling the voltage sourceto cause the ion source to produce ions and to supply the produced ionsto the ion entrance drift tube segment, and to control the ion source tostop producing ions by controlling the voltage source to cause the ionsource to stop producing ions.
 14. The ion mobility spectrometer ofclaim 12 wherein the ion gate arrangement comprises: a first ion gatepositioned in the one or another one of the plurality of cascaded drifttube segments, and a second ion gate positioned in or at the ion inletof the ion exit drift tube segment, wherein the first set of one or moreion gate signals comprises a first ion gate signal to which the firstion gate is responsive to allow ions to pass therethrough and a secondion gate signal to which the second ion gate is responsive to block ionsfrom passing therethrough, and wherein the second set of one or more iongate signals comprises a third ion gate signal to which the first iongate is responsive to block ions from passing therethrough and a fourthion gate signal to which the second ion gate is responsive to allow ionsto pass therethrough.
 15. The ion mobility spectrometer of claim 12further comprising an ion detector configured to detect ions exiting theion exit drift tube segment and produce corresponding ion detectionsignals, wherein the instructions stored in the memory further includeinstructions executable by the control circuit to process the iondetection signals to determine ion mobility spectral informationtherefrom.
 16. The ion mobility spectrometer of claim 12 wherein thepredefined ion mobility or range of ion mobilities are resonant with afundamental frequency defined by the time duration, and wherein theinstructions stored in the memory further include instructionsexecutable by the control circuit to control the number, M, of electricfield activation sources to sweep the time duration between first andsecond predefined time durations to thereby cause ions within the drifttube that have at least one of ion mobilities defined by overtonefrequencies of the time duration and ion mobilities resonant withfundamental frequencies of discrete time durations between the first andsecond time durations to travel through the drift tube.
 17. An ionmobility spectrometer instrument comprising: a linear drift tubepartitioned into a plurality of cascaded drift tube segments, eachdefining an ion inlet at one end and an ion outlet at an opposite end,with an ion elimination region defined between the ion outlet and an ioninlet of each adjacent drift tube segment, an ion source coupled to theion inlet of a first one of the plurality of cascaded drift tubesegments, a number, M, of electric field activation sources eachoperatively connected to one or more of the plurality of drift tubesegments such that, when activated, each establishes a repulsiveelectric field in at least one of the first M ion elimination regionsand in every following Mth ion elimination region, and also establishesan electric drift field in all remaining ion elimination regions and inall of the plurality of cascaded drift tube segments, a control circuitincluding a memory having instructions stored therein that areexecutable by the control circuit to sequentially activate each of thenumber, M, of electric field activation sources for a time durationwhile deactivating the remaining number, M, of electric field activationsources to thereby cause only ions supplied by the ion source that havea predefined ion mobility or range of ion mobilities defined by the timeduration to travel through the drift tube from the first drift tubesegment to a last one of the plurality of drift tube segments, and tothen, for a first predefined number of times, sequentially activatingeach of the number, M, of electric field activation sources for the timeduration while deactivating the remaining number, M, of electric fieldactivation sources in reverse order to thereby cause only ions havingthe predefined ion mobility or range of mobilities defined by the timeduration to travel through the drift tube from the last drift tubesegment to the first drift tube segment followed by sequentiallyactivating each of the number, M, of electric field activation sourcesfor the time duration while deactivating the remaining number, M, ofelectric field activation sources to thereby cause only ions having thepredefined ion mobility or range of ion mobilities defined by the timeduration to travel through the drift tube from the first drift tubesegment to the last drift tube segment, and means for randomizingpositions of the ions within the drift tube during each pass of ionsfrom at least one of the first drift tube segment to the last drift tubesegment and the last drift tube segment to the first drift tube segment.18. The ion mobility spectrometer instrument of claim 17 wherein the ioninlet of the first drift tube segment comprises an ion gate, and whereinthe instructions stored in the memory further include instructionsexecutable by the control circuit to control the ion gate to selectivelyallow entrance of ions generated by the ion source into the ion inlet ofthe first drift tube segment.
 19. The ion mobility spectrometerinstrument of claim 17 wherein the ion source comprises at least one ionseparation instrument configured to separate ions in time as a functionof one or more molecular characteristics.
 20. The ion mobilityspectrometer instrument of claim 19 wherein the at least one ionseparation instrument includes at least one of a liquid chromatograph, agas chromatograph, an ion mobility spectrometer, a mass spectrometer,and a capillary electrophoresis instrument.
 21. The ion mobilityspectrometer instrument of claim 17 further comprising an ion detectorconfigured to detect ions exiting the ion outlet of the last drift tubesegment and produce corresponding ion detection signals, wherein theinstructions stored in the memory further include instructionsexecutable by the control circuit to process the ion detection signalsto determine ion mobility spectral information therefrom.
 22. The ionmobility spectrometer of claim 17 wherein the predefined ion mobility orrange of ion mobilities is resonant with a fundamental frequency definedby the time duration, and wherein the instructions stored in the memoryfurther include instructions executable by the control circuit tocontrol the number, M, of electric field activation sources to sweep thetime duration between first and second predefined time durations tothereby cause ions within the drift tube that have at least one of ionmobilities defined by overtone frequencies of the time duration and ionmobilities resonant with fundamental frequencies of discrete timedurations between the first and second time durations to travel throughthe drift tube.
 23. A method of separating ions as a function of ionmobility in a drift tube partitioned into a plurality of cascaded drifttube segments each defining an ion inlet at one end and an ion outlet atan opposite end, with an ion elimination region defined between the ionoutlet and an ion inlet of each adjacent drift tube segment, the methodcomprising: controlling an ion source to supply ions to the ion inlet ofa first one of the plurality of drift tube segments, sequentiallycontrolling electric fields in each of the plurality of drift tubesegments and ion elimination regions for a time duration to cause onlyions supplied by the ion source to the first one of the plurality ofdrift tube segments that have a predefined ion mobility or range of ionmobilities defined by the time duration to travel through the drift tubefrom the first one of the plurality of drift tube segments to a last oneof the plurality of drift tube segments, to then, for a predefinednumber of times, sequentially control electric fields in each of theplurality of drift tube segments and ion elimination regions in reverseorder to cause only ions having the predefined ion mobility or range ofmobilities defined by the time duration to travel through the drift tubefrom the last one of the plurality of drift tube segments to the firstone of the plurality of drift tube segments drift tube segments followedby sequentially controlling electric fields in each of the plurality ofdrift tube segments and ion elimination regions to cause only ionshaving the predefined ion mobility or range of ion mobilities defined bythe time duration to travel through the drift tube from the first one ofthe plurality of drift tube segments to the last one of the plurality ofdrift tube segments, and randomizing positions of the ions within thedrift tube during each pass of ions from at least one of the first oneof the plurality of drift tube segments to the last one of the pluralityof drift tube segments and the last one of the plurality of drift tubesegments to the first one of the plurality of drift tube segments. 24.The method of claim 23 wherein randomizing positions of the ions withinthe drift tube comprises trapping the ions for a trap period in an iontrap positioned within the drift tube during each pass of the ions, thetrap period selected to allow ions trapped within the ion trap torandomize their positions relative to the ion trap.
 25. The method ofclaim 23 wherein randomizing positions of the ions within the drift tubecomprises trapping the ions for a trap period in a first ion trappositioned adjacent to the last one of the plurality of drift tubesegments during each pass of the ions from the first one of theplurality of drift tube segments to the last one of the plurality ofdrift tube segments and trapping the ions for the trap period in asecond ion trap positioned adjacent to the first one of the plurality ofdrift tube segments during each pass of the ions from the last one ofthe plurality of drift tube segments to the first one of the pluralityof drift tube segments, the trap period selected to allow ions trappedwithin the first and second ion traps to randomize their positionsrelative to the first and second ion traps respectively.
 26. The methodof claim 23 wherein randomizing positions of the ions within the drifttube comprises progressively diminishing magnitudes of the electricfields in a number of adjacent ones of the plurality of drift tubesegments to cause the ions to randomize by bunching up in at least someof the number of adjacent ones of the plurality of drift tube segmentsin which the magnitudes of the electric fields are diminished.
 27. Themethod of claim 26 wherein the number of adjacent ones of the pluralityof drift tube segments comprises a first subset of adjacent ones of theplurality of drift tube segments including the first one of theplurality of drift tube segments and a second subset of adjacent ones ofthe plurality of drift tube segments including the last one of theplurality of drift tube segments.
 28. The method of claim 26 wherein thenumber of adjacent ones of the plurality of drift tube segments includesat least one of the first one of the plurality of drift tube segmentsand the last one of the plurality of drift tube segments.
 29. The methodof claim 23 wherein the predefined ion mobility or range of ionmobilities is resonant with a fundamental frequency defined by the timeduration, and wherein the method further comprises controlling thenumber, M, of electric field activation sources to sweep the timeduration between first and second predefined time durations to therebycause ions within the drift tube that have at least one of ionmobilities defined by overtone frequencies of the time duration and ionmobilities resonant with fundamental frequencies of discrete timedurations between the first and second time durations to travel throughthe drift tube.
 30. An ion mobility spectrometer instrument comprising:a linear drift tube partitioned into a plurality of cascaded drift tubesegments, each defining an ion inlet at one end and an ion outlet at anopposite end, with an ion elimination region defined between the ionoutlet and an ion inlet of each adjacent drift tube segment, an ionsource coupled to the ion inlet of a first one of the plurality ofcascaded drift tube segments, an ion trap positioned to receive thereinions traveling through the drift tube, a number, M, of electric fieldactivation sources each operatively connected to one or more of theplurality of drift tube segments such that, when activated, eachestablishes a repulsive electric field in at least one of the first Mion elimination regions and in every following Mth ion eliminationregion, and also establishes an electric drift field in all remainingion elimination regions and in all of the plurality of cascaded drifttube segments, and a control circuit including a memory havinginstructions stored therein that are executable by the control circuitto, for a first predefined number of times, sequentially activate eachof the number, M, of electric field activation sources for a timeduration while deactivating the remaining number, M, of electric fieldactivation sources to thereby cause only ions supplied by the ion sourcethat have a predefined ion mobility or range of ion mobilities definedby the time duration to travel through the drift tube followed bycontrolling the ion trap to trap therein the ions traveling through thedrift tube that have the predefined ion mobility or range of ionmobilities, and to then, for a second predefined number of times,control the ion trap to release the ions trapped therein, tosequentially activate each of the number, M, of electric fieldactivation sources for the time duration while deactivating theremaining number, M, of electric field activation sources to cause thereleased ions having the predefined ion mobility or range of ionmobilities to travel from to one end of the linear drift tube, then backto the other end of the linear drift tube and back to the ion trapfollowed by controlling the ion trap to trap the ions therein for a trapperiod selected to allow ions trapped within the ion trap to randomizetheir positions relative to the ion trap, and to then control the iontrap to release the ions trapped therein to an ion detector.
 31. The ionmobility spectrometer of claim 30 further comprising a voltage supplyoperatively connected to the ion source and to the control circuit,wherein the instructions stored in the memory further includeinstructions executable by the control circuit to control the voltagesource each of the first predefined number of times to cause the ionsource to produce ions and supply the produced ions to the ion inlet ofthe first one of the plurality of drift tube segments.
 32. The ionmobility spectrometer of claim 30 further comprising a voltage supplyoperatively connected to the ion source and to the control circuit,wherein the instructions stored in the memory further includeinstructions executable by the control circuit to control the voltagesource to cause the ion source to continuously produce ions and supplythe produced ions to the ion inlet of the first one of the plurality ofdrift tube segments.
 33. The ion mobility spectrometer of claim 30wherein the ion detector is configured to detect ions released from thefirst ion trap and produce corresponding ion detection signals, whereinthe instructions stored in the memory further include instructionsexecutable by the control circuit to process the ion detection signalsto determine ion mobility spectral information therefrom.
 34. The ionmobility spectrometer of claim 30 wherein the plurality of cascadeddrift tube segments comprises a last drift tube segment at an oppositeend of the drift tube from the first drift tube segment, and wherein theion trap is coupled to the ion outlet of the last drift tube segment.35. The ion mobility spectrometer of claim 30 wherein the predefined ionmobility or range of ion mobilities is resonant with a fundamentalfrequency defined by the time duration, and wherein the instructionsstored in the memory further include instructions executable by thecontrol circuit to control the number, M, of electric field activationsources during the first predefined time period and during the secondpredefined time period to sweep the time duration between first andsecond predefined time durations to thereby cause ions within the drifttube that have at least one of ion mobilities defined by overtonefrequencies of the time duration and ion mobilities resonant withfundamental frequencies of discrete time durations between the first andsecond time durations to travel through the drift tube.
 36. The ionmobility spectrometer of claim 35 further comprising a voltage supplyoperatively connected to the ion source and to the control circuit,wherein the instructions stored in the memory further includeinstructions executable by the control circuit to control the voltagesource each of the first predefined number of times to cause the ionsource to produce ions and supply the produced ions to the ion inlet ofthe first one of the plurality of drift tube segments.
 37. The ionmobility spectrometer of claim 35 further comprising a voltage supplyoperatively connected to the ion source and to the control circuit,wherein the instructions stored in the memory further includeinstructions executable by the control circuit to control the voltagesource to cause the ion source to continuously produce ions and supplythe produced ions to the ion inlet of the first one of the plurality ofdrift tube segments.
 38. An ion mobility spectrometer instrumentcomprising: a linear drift tube, an ion source coupled to the ion inletof the linear drift tube, a first ion trap positioned adjacent to theion inlet of the linear drift tube, a second ion trap positionedadjacent to an ion outlet of the linear drift tube, the linear drifttube defining a single drift tube region between the first and secondion traps, at least one electric field activation source operativelyconnected to the single drift tube region, the at least one electricfield activation source controllable to establish an electric field inthe single drift tube region in a first direction that causes ionssupplied by the ion source to drift from the first ion trap toward thesecond ion trap and controllable to alternatively establish an electricdrift field in the single drift tube region in a second direction thatcauses ions supplied by the ion source to drift from the second ion traptoward the first ion trap, and a control circuit including a memoryhaving instructions stored therein that are executable by the controlcircuit to execute a process a predefined number of times, the processincluding activating the at least one electric field activation sourcefor a time duration to establish an electric field in the firstdirection to cause only ions supplied by the ion source that have apredefined ion mobility or range of ion mobilities defined by the timeduration to travel through the single drift tube region in the firstdirection toward the second ion trap followed by controlling the secondion trap to trap therein the ions that have the predefined ion mobilityor range of ion mobilities, and then controlling the second ion trap torelease the ions trapped therein and activate the at least one electricfield activation source for the time duration to establish an electricfield in the second direction to cause only ions supplied by the ionsource that have the predefined ion mobility or range of ion mobilitiesdefined by the time duration to travel through the single drift tuberegion in the second direction toward the first ion trap followed bycontrolling the first ion trap to trap therein the ions that have thepredefined ion mobility or range of ion mobilities followed bycontrolling the first ion trap to release the ions trapped therein. 39.The ion mobility spectrometer of claim 38 wherein the instructionsstored in the memory further include instructions executable by thecontrol circuit to control the first and second ion traps to trap ionstherein for a trap period, the trap period selected to allow ionstrapped within the first ion trap and the second ion trap to randomizetheir positions relative to the first and second ion trap respectively.40. The ion mobility spectrometer instrument of claim 38 furthercomprising an ion detector configured to detect ions exiting the lineardrift tube, wherein the instructions stored in the memory furtherinclude instructions executable by the control circuit to control thesecond ion trap to release ions trapped therein toward the ion detectorand to process the ion detection signals to determine ion mobilityspectral information therefrom.
 41. The ion mobility spectrometer ofclaim 38 wherein the predefined ion mobility or range of ion mobilitiesis resonant with a fundamental frequency defined by the time duration,and wherein the instructions stored in the memory further includeinstructions executable by the control circuit to control the at leastone electric field activation source to sweep the time duration betweenfirst and second predefined time durations to thereby cause ions thathave fundamental frequencies resonant with each of a number of discretetime durations between the first and second time durations to travelthrough the single drift tube region, and to execute the process thepredefined number of times for each of the number of discrete timedurations between the first and second predefined time durations.